Study to Find a Safe Dose and Show Early Clinical Activity of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent/ Refractory Solid Tumors

Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01962103
Collaborator
(none)
107
20
10
59.1
5.4
0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.

Detailed Description

ABI-007-PST-001 is a Phase 1/2, multicenter, open-label, dose-finding study to assess the safety , tolerability, and preliminary efficacy of weekly nab-paclitaxel in pediatric patients with recurrent or refractory solid tumors (excluding brain tumors). The Phase 1 portion of the study, with a dose escalation design, ended and the recommended Phase 2 dose (RP2D) was determined as 240 mg/m^2 intravenously (IV) in patients weighing > 10 kg and 11.5 mg/kg in patients weighing ≤ 10 kg, on Days 1, 8 and 15 of a 28-day cycle. The Phase 2 portion of the study will enroll additional patients at the RP2D into 1 of 3 solid tumor groups [neuroblastomas, rhabdomyosarcomas, Ewing's sarcomas]. Both phases of the study are open-label and conducted at multiple centers.

The Phase 2 is using a Simon 2-stage design to monitor patient enrollment for each group separately. The rhabdomyosarcoma group, neuroblastoma or Ewing's sarcoma groups did not reach the expected number of 2 responders out of 14 efficacy eligible patients. Consequently, the groups were stopped.

Study Design

Study Type:
Interventional
Actual Enrollment :
107 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, Multicenter, Open-label, Dose-finding Study to Assess the Safety, Tolerability, and Preliminary Efficacy of Weekly Nab-paclitaxel in Pediatric Patients With Recurrent or Refractory Solid Tumors.
Actual Study Start Date :
Dec 4, 2013
Actual Primary Completion Date :
Dec 5, 2017
Actual Study Completion Date :
Nov 6, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: nab-paclitaxel

nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.

Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Other Names:
  • Abraxane
  • Experimental: Phase 1: Nab-Paclitaxel 120 mg/m^2

    nab-paclitaxel 120 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 1: Nab-Paclitaxel 150 mg/m^2

    nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 1: Nab-Paclitaxel 180 mg/m^2

    nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 1: Nab-Paclitaxel 210 mg/m^2

    nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 1: Nab-Paclitaxel 240 mg/m^2

    nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 1: Nab-Paclitaxel 270 mg/m^2

    nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 2: Ewing's Sarcoma

    Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 2: Neuroblastoma

    Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Experimental: Phase 2: Rhabdomyosarcoma

    Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.

    Drug: nab-paclitaxel
    IV infusion
    Other Names:
  • Abraxane
  • Outcome Measures

    Primary Outcome Measures

    1. Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) [DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations]

      A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted > 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted > 7 days or required transfusion > 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting > 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay > 21 days. Use of "..." in the table rows signifies the continuation of row title per the above list.

    2. Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.]

      An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0.

    3. Phase 2: Overall Response Rate (ORR) [Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).]

      Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.

    Secondary Outcome Measures

    1. Phase 1: ORR [Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.]

      Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.

    2. Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

    3. Phase 1: Cmax - Dose-Normalized [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

    4. Phase 1: Area Under the Plasma Concentration-Time Curve (AUC) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).

    5. Phase 1: AUC - Dose-Normalized [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Measurements include: AUC24 and AUCinf.

    6. Phase 1: Clearance (CL) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Measurement of renal clearance from the body.

    7. Phase 1: CL - Body Surface Area (BSA)-Normalized [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Measurement of renal clearance from the body.

    8. Phase 1: Volume of Distribution (Vss) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

    9. Phase 1: Vss - BSA-Normalized [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

    10. Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.

    11. Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.

    12. Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling.

    13. Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.

    14. Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.

    15. Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.

    16. Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3) [Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)]

      Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.

    17. Phase 2: Duration of Response (DOR) [Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.]

      Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)

    18. Phase 2: Disease Control Rate (DCR) [Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).]

      Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.

    19. Phase 2: Progression-Free Survival (PFS) [Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.]

      PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method.

    20. Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year [1 year]

      Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.

    21. Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.]

      An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    6 Months to 24 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must meet all of the following criteria to be enrolled in the study:
    1. Patient has a confirmed solid tumor diagnosis according to the

    following:

    1. Phase 1: patient has a recurrent or refractory solid tumor that has

    progressed or did not respond to standard therapy, or for which no

    standard anticancer therapy exists

    1. Phase 2: patient has radiologically documented measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (for neuroblastoma, evaluable disease by 123^I-metaiodobenzylguanidine [MIBG]/Curie score is also acceptable) in 1 of the following tumor types and has failed up to 3 lines of treatment: Group 1: neuroblastoma, Group 2: rhabdomyosarcoma; Group 3: Ewing's sarcoma.

    2. The patient has a Lansky/Karnofsky performance status score of ≥ 70%.

    3. The patient has adequate serum chemistry levels, evidenced by the

    following laboratory values

    1. aspartate aminotransferase (AST)/serum glutamic-oxaloacetric

    transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic

    pyruvate transaminase (SGPT) ≤ 2.5 × upper limit of normal range (ULN)

    1. Total bilirubin ≤ 1.5 × ULN

    2. Creatinine ≤ 1.5 × ULN

    3. The patient has adequate bone marrow function, evidenced by the

    following:

    1. Absolute neutrophil count ≥ 1.0 × 10^9 cells/L

    2. Platelets ≥ 80 × 10^9 cells/L (transfusion independent, defined as not

    receiving platelet transfusions within 7 days prior to laboratory sample). In the phase 2 portion, for patients with known bone marrow involvement, platelets ≥ 50 × 10^9 cells/L

    1. Hemoglobin ≥ 8 g/dL (transfusion is permitted to fulfill this criterion).

    2. The patient (when applicable) or patient's parent(s) or legal guardian(s)

    understand(s) and voluntarily signed an informed consent document prior

    to any study-related assessments/procedures being conducted. Where

    locally applicable, the patient also understands and voluntarily provides

    his/her assent prior to any study-related assessments/procedures being

    conducted.

    1. Male patients of childbearing potential must use a condom during

    sexual intercourse and shall not father a child during the study and for 6 months after the last dose of study medication.

    1. Female patients of childbearing potential [defined as all female

    patients ≥ 12 years old or who have reached menarche, whichever occurs

    first] must have both of the following:

    1. Agree to the use of two physician-approved contraceptive methods

    simultaneously or practice complete abstinence while on study medication or for a longer period if required by regulations.

    1. True abstinence: When this is in line with the preferred and usual

    lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,

    symptothermal, postovulation methods) and withdrawal are not

    acceptable methods of contraception.

    1. Acceptable contraceptive methods include: oral, injectable, or

    implantable hormonal contraceptive; tubal ligation; intra-uterine device;

    barrier contraceptive with spermicide; or vasectomized partner) including

    at least one barrier method.

    1. Have negative serum pregnancy test result at screening confirmed by

    negative urine pregnancy dipstick within 72 hours prior to first dose of

    investigational product (if serum test occurred > 72 hours from first

    dose); pregnancy test with sensitivity of at least 25 mIU/mL.

    Exclusion Criteria:
    • The presence of any of the following will exclude a patient from enrollment:
    1. The patient has a primary brain tumor(s) or brain metastasis (unless metastasis is treated and stable for > 28 days). In patients who are symptomatic, a brain scan is required to exclude metastasis.

    2. The patient has received therapeutic dose chemotherapy or radiotherapy ≤ 21 days prior to start of investigational product.

    3. The patient has received maintenance dose chemotherapy (e.g., low dose cyclophosphamide) ≤ 7 days from the first dose of investigational product.

    4. The patient has received any investigational therapy ≤ 28 days prior to start of investigational product. Investigational therapy is defined as any medicinal product that is not approved in the country of treatment for any indication, adult or pediatric.

    5. The patient has received any biological therapy ≤ 7 days prior to the start of investigational product, or monoclonal antibody ≤ 3 half-lives or 28 days, whichever is shorter, prior to the first dose of investigational product.

    6. The patient has received any hematopoietic stem cell transplantation (HSCT) ≤ 3 months prior to start of investigational product.

    7. The patient has received allogeneic hematopoietic stem cell transplantation (HSCT) ≤ 3 months or autologous HSCT ≤ 21 days prior to start of investigational product.

    8. The patient has not recovered from the acute toxic effects of prior chemotherapy, radiation, or major surgery/significant trauma.

    9. The patient has had minor surgery ≤ 7 days from the start of study treatment (excluding the placement of central/peripheral lines, skin biopsy).

    10. The patient has a known history of stroke, myocardial infarction, peripheral vascular disease, or recent (within 3 months) uncontrolled deep venous thrombosis.

    11. The patient has a known history or current diagnosis of human immunodeficiency virus (HIV) infection, regardless of treatment status.

    12. The patient has an uncontrolled intercurrent illness including but not limited to ongoing or active infection requiring antibiotic, antifungal, or antiviral therapy, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

    13. The patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study.

    14. The patient has any condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk if he/she were to participate in the study.

    15. The patient has any condition that confounds the ability to interpret data from the study.

    16. The patient or parent(s)/guardian(s) is/are unable to comply with the study visit schedule and other protocol requirements, in the opinion of the investigator.

    17. The patient has ≥ Grade 2 peripheral neuropathy by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) at screening.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    2 Columbia University Medical Center New York New York United States 10032
    3 The Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    4 Institute for Pediatric Hematology - Oncology, Leon Berard Cancer Center Lyon France 69008
    5 Hopital d'Enfants, CHU Nancy Nancy France 54000
    6 Institut Curie Paris France 75005
    7 Institut Gustave Roussy Villejuif France 94805
    8 Azienda Ospedaliera Universitaria Meyer Firenze Italy 50139
    9 Children's Hospital Largo Genova Italy 16147
    10 Istituto Nazionale Tumori Milan Italy
    11 Clinica di Oncoematologia Padova Italy 35128
    12 Policlinico Agostino Gemelli Rome Italy 00168
    13 l'Azienda Ospedaliera Regina Margherita - Sant Anna Torino Italy 10126
    14 Hospital Universitario Vall D Hebron Barcelona Spain 8035
    15 Hospital Sant Joan de Deu Barcelona Spain 8950
    16 Spanish National Cancer Research Centre Madrid Spain 28029
    17 Hospital Universitario Virgen Del Rocio Sevilla Spain 41013
    18 Unidad de Oncologia Pediatrica, Hospital Universitario la Fe Valencia Spain 46026
    19 Universitäts-Kinderklinik Zurich Switzerland 8032
    20 Royal Marsden Hospital Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Ileana Elias, M.D., Celgene Corporation

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01962103
    Other Study ID Numbers:
    • ABI-007-PST-001
    First Posted:
    Oct 14, 2013
    Last Update Posted:
    Dec 27, 2019
    Last Verified:
    Dec 1, 2019

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Sixty-five participants were included in the Phase 1 enrolled population, and 64 enrolled partcipants received at least 1 dose of study drug and were included in the safety population, noted below. Forty-two participants were included in the Phase 2 enrolled and safety populations.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Period Title: Phase 1
    STARTED 16 8 14 11 8 7 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 16 8 14 11 8 7 0 0 0
    Period Title: Phase 1
    STARTED 0 0 0 0 0 0 14 14 14
    COMPLETED 0 0 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 0 14 14 14

    Baseline Characteristics

    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma Total
    Arm/Group Description nab-paclitaxel 120 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Total of all reporting groups
    Overall Participants 16 8 14 11 8 7 14 14 14 106
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    11.7
    (3.32)
    12.1
    (5.84)
    10.2
    (4.64)
    10.2
    (5.36)
    11.6
    (4.63)
    12.1
    (2.97)
    10.1
    (4.63)
    7.1
    (3.42)
    12.4
    (6.42)
    10.7
    (4.81)
    Sex: Female, Male (Count of Participants)
    Female
    9
    56.3%
    4
    50%
    9
    64.3%
    7
    63.6%
    1
    12.5%
    3
    42.9%
    6
    42.9%
    5
    35.7%
    9
    64.3%
    53
    50%
    Male
    7
    43.8%
    4
    50%
    5
    35.7%
    4
    36.4%
    7
    87.5%
    4
    57.1%
    8
    57.1%
    9
    64.3%
    5
    35.7%
    53
    50%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    12.5%
    3
    37.5%
    1
    7.1%
    1
    9.1%
    3
    37.5%
    0
    0%
    0
    0%
    2
    14.3%
    5
    35.7%
    17
    16%
    Not Hispanic or Latino
    6
    37.5%
    5
    62.5%
    7
    50%
    10
    90.9%
    5
    62.5%
    5
    71.4%
    11
    78.6%
    8
    57.1%
    8
    57.1%
    65
    61.3%
    Unknown or Not Reported
    8
    50%
    0
    0%
    6
    42.9%
    0
    0%
    0
    0%
    2
    28.6%
    3
    21.4%
    4
    28.6%
    1
    7.1%
    24
    22.6%
    Race/Ethnicity, Customized (Count of Participants)
    White
    11
    68.8%
    8
    100%
    9
    64.3%
    9
    81.8%
    8
    100%
    5
    71.4%
    11
    78.6%
    11
    78.6%
    12
    85.7%
    84
    79.2%
    Not Collected or Reported
    5
    31.3%
    0
    0%
    5
    35.7%
    0
    0%
    0
    0%
    1
    14.3%
    3
    21.4%
    3
    21.4%
    1
    7.1%
    18
    17%
    Other, Not Specified
    0
    0%
    0
    0%
    0
    0%
    2
    18.2%
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    3
    2.8%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.1%
    1
    0.9%
    Participants With Any Prior Cancer Treatment (Count of Participants)
    Any Prior Cancer Treatment
    16
    100%
    8
    100%
    14
    100%
    11
    100%
    8
    100%
    7
    100%
    14
    100%
    14
    100%
    14
    100%
    106
    100%
    Prior Radiation Therapy
    9
    56.3%
    4
    50%
    11
    78.6%
    7
    63.6%
    6
    75%
    6
    85.7%
    12
    85.7%
    10
    71.4%
    10
    71.4%
    75
    70.8%
    Prior Cancer Surgeries
    14
    87.5%
    7
    87.5%
    9
    64.3%
    9
    81.8%
    5
    62.5%
    7
    100%
    10
    71.4%
    11
    78.6%
    6
    42.9%
    78
    73.6%
    Prior Systemic Anticancer Therapy
    16
    100%
    8
    100%
    14
    100%
    11
    100%
    8
    100%
    7
    100%
    14
    100%
    14
    100%
    14
    100%
    106
    100%
    Prior Systemic Anticancer Regimens
    16
    100%
    8
    100%
    14
    100%
    11
    100%
    8
    100%
    7
    100%
    14
    100%
    14
    100%
    14
    100%
    106
    100%
    Prior Stem Cell Transplants
    2
    12.5%
    2
    25%
    3
    21.4%
    2
    18.2%
    3
    37.5%
    2
    28.6%
    3
    21.4%
    10
    71.4%
    0
    0%
    27
    25.5%
    Other Prior Anticancer Therapies
    2
    12.5%
    0
    0%
    1
    7.1%
    3
    27.3%
    2
    25%
    0
    0%
    1
    7.1%
    6
    42.9%
    0
    0%
    15
    14.2%
    Number of Prior Systemic Anticancer Regimens Received (systemic anticancer regimens) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [systemic anticancer regimens]
    3.69
    (1.815)
    3.25
    (1.832)
    3.64
    (1.946)
    3.64
    (2.461)
    3.00
    (1.309)
    3.00
    (0.816)
    2.50
    (0.519)
    2.14
    (0.663)
    2.21
    (0.579)
    2.99
    (1.552)

    Outcome Measures

    1. Primary Outcome
    Title Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
    Description A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted > 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted > 7 days or required transfusion > 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting > 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay > 21 days. Use of "..." in the table rows signifies the continuation of row title per the above list.
    Time Frame DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations

    Outcome Measure Data

    Analysis Population Description
    Dose Determining Set (DDS): all Phase 1 participants who received all 3 weekly doses of nab-paclitaxel at the cohort planned dose during Cycle 1 and had adequate safety assessments during the DLT assessment period or experienced a DLT. The DDS did not include participants who were enrolled at each dose once the dose had been determined to be safe.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 6 6 6 6 6 7
    At least 1 DLT
    1
    6.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    Gr 3/4 Nonhematologic Toxicity...
    1
    6.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Gr 3/4 Nausea or Vomiting Persisting >5 days...
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Gr 4 Thrombocytopenia/Anemia Persisting >7 days...
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Gr 3 Thrombocytopenia with Bleeding
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Gr 4 Uncomplicated Neutropenia Lasting >7 days
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    Febrile Neutropenia+Confirmed Bacterial Infection
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Gr3 Hematologic Toxicity Requiring Tx Delay...
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
    Description An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0.
    Time Frame Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all participants who took at least 1 dose of study drug.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 16 8 14 11 8 7
    TEAE
    16
    100%
    8
    100%
    14
    100%
    11
    100%
    8
    100%
    7
    100%
    Treatment-related (TR) TEAE
    14
    87.5%
    8
    100%
    12
    85.7%
    11
    100%
    7
    87.5%
    7
    100%
    Grade 3 or 4 TEAE
    13
    81.3%
    8
    100%
    10
    71.4%
    10
    90.9%
    8
    100%
    7
    100%
    TR Grade 3 or 4 TEAE
    9
    56.3%
    7
    87.5%
    7
    50%
    9
    81.8%
    7
    87.5%
    7
    100%
    Serious TEAE
    10
    62.5%
    7
    87.5%
    6
    42.9%
    5
    45.5%
    3
    37.5%
    4
    57.1%
    TR Serious TEAE
    1
    6.3%
    4
    50%
    4
    28.6%
    2
    18.2%
    1
    12.5%
    3
    42.9%
    TEAE Leading to Drug Discontinuation
    4
    25%
    0
    0%
    2
    14.3%
    1
    9.1%
    2
    25%
    2
    28.6%
    TR TEAE Leading to Drug Discontinuation
    1
    6.3%
    0
    0%
    0
    0%
    1
    9.1%
    2
    25%
    2
    28.6%
    TEAE Leading to Dose Reduction
    0
    0%
    1
    12.5%
    2
    14.3%
    1
    9.1%
    3
    37.5%
    3
    42.9%
    TR TEAE Leading to Dose Reduction
    0
    0%
    1
    12.5%
    2
    14.3%
    1
    9.1%
    3
    37.5%
    3
    42.9%
    TEAE Leading to Drug Interruption
    2
    12.5%
    2
    25%
    3
    21.4%
    4
    36.4%
    3
    37.5%
    2
    28.6%
    TR TEAE Leading to Drug Interruption
    0
    0%
    2
    25%
    1
    7.1%
    3
    27.3%
    3
    37.5%
    2
    28.6%
    TEAE Leading to Death
    2
    12.5%
    1
    12.5%
    0
    0%
    0
    0%
    1
    12.5%
    1
    14.3%
    TR TEAE Leading to Death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Primary Outcome
    Title Phase 2: Overall Response Rate (ORR)
    Description Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.
    Time Frame Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
    Arm/Group Title Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 13 14 14
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    0
    0%
    7.1
    50.7%
    4. Secondary Outcome
    Title Phase 1: ORR
    Description Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
    Time Frame Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Population: participants who met eligibility criteria for Phase 1, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 14 8 12 10 8 7
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    12.5
    156.3%
    14.3
    204.3%
    5. Secondary Outcome
    Title Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax)
    Description
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) population: all participannts who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 13 7 12 9 7 6
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    3488
    (73.7)
    5468
    (38.0)
    5597
    (33.4)
    5616
    (63.9)
    7831
    (23.1)
    8078
    (41.5)
    6. Secondary Outcome
    Title Phase 1: Cmax - Dose-Normalized
    Description
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 13 7 12 9 7 6
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL/[mg]]
    23.3
    (87.5)
    25.4
    (46.6)
    27.3
    (47.3)
    23.2
    (80.3)
    28.2
    (48.7)
    21.0
    (46.6)
    7. Secondary Outcome
    Title Phase 1: Area Under the Plasma Concentration-Time Curve (AUC)
    Description Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data for given measure.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 13 7 12 9 7 6
    AUCt
    7844
    (73.4)
    10374
    (91.8)
    9690
    (37.1)
    11817
    (64.0)
    12706
    (29.2)
    11245
    (22.6)
    AUC24
    6392
    (79.0)
    8944
    (85.9)
    8365
    (37.7)
    10932
    (66.3)
    11167
    (27.4)
    9768
    (20.7)
    AUCinf
    8867
    (85.4)
    11992
    (99.8)
    10087
    (38.4)
    14361
    (72.1)
    14242
    (29.2)
    12424
    (28.5)
    8. Secondary Outcome
    Title Phase 1: AUC - Dose-Normalized
    Description Measurements include: AUC24 and AUCinf.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data for given measure.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 13 7 12 8 7 6
    AUC24
    42.7
    (77.4)
    41.6
    (87.0)
    40.8
    (39.7)
    43.3
    (63.6)
    40.2
    (65.4)
    25.4
    (26.1)
    AUCinf
    62.0
    (75.7)
    49.2
    (101)
    47.8
    (39.8)
    64.8
    (25.4)
    52.3
    (67.4)
    31.3
    (34.9)
    9. Secondary Outcome
    Title Phase 1: Clearance (CL)
    Description Measurement of renal clearance from the body.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 9 6 10 6 6 5
    Geometric Mean (Geometric Coefficient of Variation) [L/h]
    16.1
    (75.6)
    20.3
    (101)
    20.9
    (39.9)
    15.4
    (25.4)
    19.1
    (67.4)
    31.9
    (35.0)
    10. Secondary Outcome
    Title Phase 1: CL - Body Surface Area (BSA)-Normalized
    Description Measurement of renal clearance from the body.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 9 6 10 6 6 5
    Geometric Mean (Geometric Coefficient of Variation) [L/h/m^2]
    13.5
    (85.1)
    12.5
    (99.3)
    17.8
    (38.3)
    14.6
    (72.3)
    16.7
    (29.2)
    21.8
    (28.4)
    11. Secondary Outcome
    Title Phase 1: Volume of Distribution (Vss)
    Description
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 9 6 10 6 6 5
    Geometric Mean (Geometric Coefficient of Variation) [liters]
    127
    (145)
    266
    (78.3)
    146
    (106)
    89.8
    (45.1)
    175
    (117)
    446
    (17.6)
    12. Secondary Outcome
    Title Phase 1: Vss - BSA-Normalized
    Description
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
    Measure Participants 9 6 10 6 6 5
    Geometric Mean (Geometric Coefficient of Variation) [L/m^2]
    106
    (95.3)
    164
    (78.4)
    124
    (82.8)
    84.9
    (49.7)
    154
    (56.5)
    304
    (29.0)
    13. Secondary Outcome
    Title Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1)
    Description Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title PK Population
    Arm/Group Description Phase 1: nab-paclitaxel 120-270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Phase 2: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 106
    Number [liters]
    11.8
    14. Secondary Outcome
    Title Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL)
    Description Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data
    Arm/Group Title PK Population
    Arm/Group Description The PK population included all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Measure Participants 106
    Number [μg/h]
    31983
    15. Secondary Outcome
    Title Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL)
    Description Population PK analysis was performed using nonlinear mixed effect modeling.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data
    Arm/Group Title PK Population
    Arm/Group Description Phase 1: nab-paclitaxel 120-270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Phase 2: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 106
    Number [μg/L]
    951
    16. Secondary Outcome
    Title Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2)
    Description Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title PK Population
    Arm/Group Description Phase 1: nab-paclitaxel 120-270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Phase 2: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 106
    Number [L/h]
    22.4
    17. Secondary Outcome
    Title Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3)
    Description Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title PK Population
    Arm/Group Description Phase 1: nab-paclitaxel 120-270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Phase 2: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 106
    Number [L/h]
    34.8
    18. Secondary Outcome
    Title Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2)
    Description Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title PK Population
    Arm/Group Description Phase 1: nab-paclitaxel 120-270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Phase 2: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 106
    Number [liters]
    545
    19. Secondary Outcome
    Title Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3)
    Description Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.
    Time Frame Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)

    Outcome Measure Data

    Analysis Population Description
    PK population: all participants who received at least one dose of nab-paclitaxel and had evaluable concentration data.
    Arm/Group Title PK Population
    Arm/Group Description Phase 1: nab-paclitaxel 120-270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Phase 2: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 106
    Number [liters]
    45.3
    20. Secondary Outcome
    Title Phase 2: Duration of Response (DOR)
    Description Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)
    Time Frame Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Population: participants (with response) who met eligibility criteria for Phase 2, completed ≥ 1 dose of study drug, and had baseline and ≥ 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
    Arm/Group Title Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 0 0 1
    Median (Full Range) [weeks]
    6.14
    21. Secondary Outcome
    Title Phase 2: Disease Control Rate (DCR)
    Description Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
    Time Frame Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
    Arm/Group Title Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 13 14 14
    Number (95% Confidence Interval) [percentage of participants]
    30.8
    192.5%
    7.1
    88.8%
    7.1
    50.7%
    22. Secondary Outcome
    Title Phase 2: Progression-Free Survival (PFS)
    Description PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method.
    Time Frame Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed at least 1 dose of study drug, and had baseline and at least 1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
    Arm/Group Title Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 13 14 14
    Median (95% Confidence Interval) [weeks]
    13
    7.4
    5.1
    23. Secondary Outcome
    Title Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year
    Description Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
    Time Frame 1 year

    Outcome Measure Data

    Analysis Population Description
    Efficacy Evaluable Population: participants who met eligibility criteria for Phase 2, completed ≥1 dose of study drug, and had baseline and ≥1 postbaseline efficacy assessment if having not discontinued the investigational product prior to postbaseline efficacy assessment due to disease progression or systematic deterioration.
    Arm/Group Title Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 13 14 14
    Number (95% Confidence Interval) [percentage of participants]
    48
    300%
    25
    312.5%
    15
    107.1%
    24. Secondary Outcome
    Title Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
    Description An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
    Time Frame Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all participants who took at least 1 dose of study drug.
    Arm/Group Title Phase 2: Ewing's Sarcoma Phase 2: Neuroblastoma Phase 2: Rhabdomyosarcoma
    Arm/Group Description Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity. Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    Measure Participants 14 14 14
    TEAE
    14
    87.5%
    14
    175%
    14
    100%
    Treatment-related (TR) TEAE
    13
    81.3%
    12
    150%
    12
    85.7%
    Grade 3 or 4 TEAE
    12
    75%
    13
    162.5%
    12
    85.7%
    TR Grade 3 or 4 TEAE
    9
    56.3%
    9
    112.5%
    10
    71.4%
    Serious TEAE
    6
    37.5%
    6
    75%
    11
    78.6%
    TR Serious TEAE
    2
    12.5%
    2
    25%
    6
    42.9%
    TEAE Leading to Drug Discontinuation
    3
    18.8%
    1
    12.5%
    3
    21.4%
    TR TEAE Leading to Drug Discontinuation
    1
    6.3%
    0
    0%
    3
    21.4%
    TEAE Leading to Dose Reduction
    4
    25%
    5
    62.5%
    4
    28.6%
    TR TEAE Leading to Dose Reduction
    4
    25%
    4
    50%
    4
    28.6%
    TEAE Leading to Drug Interruption
    5
    31.3%
    3
    37.5%
    4
    28.6%
    TR TEAE Leading to Drug Interruption
    3
    18.8%
    3
    37.5%
    2
    14.3%
    TEAE Leading to Death
    0
    0%
    2
    25%
    3
    21.4%
    TR TEAE Leading to Death
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), rhabdomyosarcoma = 5 weeks (1-13).
    Adverse Event Reporting Description All participants in both portions of the study were followed for 28 days after discontinuing treatment for safety and monitoring of AEs. AE's were analyzed in terms of TEAEs, which were defined as any AEs that began or worsened in severity on or after the start of study drug through 28 days after the last dose of study drug.
    Arm/Group Title Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Nab-Paclitaxel 240 mg/m^2
    Arm/Group Description nab-paclitaxel 120 mg/m^2 intravenously (IV) on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the recommended phase 2 dose (RP2D). nab-paclitaxel 150 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 180 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 210 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 240 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. nab-paclitaxel 270 mg/m^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D. Participants with Ewing's sarcoma, neuroblastoma, or rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m^2 in participants weighing > 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
    All Cause Mortality
    Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Nab-Paclitaxel 240 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/16 (87.5%) 7/8 (87.5%) 11/14 (78.6%) 5/11 (45.5%) 8/8 (100%) 5/7 (71.4%) 25/42 (59.5%)
    Serious Adverse Events
    Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Nab-Paclitaxel 240 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 10/16 (62.5%) 7/8 (87.5%) 6/14 (42.9%) 5/11 (45.5%) 3/8 (37.5%) 4/7 (57.1%) 23/42 (54.8%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 4/42 (9.5%)
    Leukopenia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Neutropenia 1/16 (6.3%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Thrombocytopenia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Cardiac disorders
    Tachycardia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Diarrhoea 1/16 (6.3%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Nausea 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Vomiting 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    General disorders
    Chills 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    General physical health deterioration 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 4/42 (9.5%)
    Generalised oedema 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Oedema peripheral 1/16 (6.3%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pyrexia 0/16 (0%) 3/8 (37.5%) 2/14 (14.3%) 3/11 (27.3%) 1/8 (12.5%) 2/7 (28.6%) 6/42 (14.3%)
    Infections and infestations
    Cellulitis 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Device related infection 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Gastroenteritis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Lower respiratory tract infection bacterial 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Pneumonia 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Soft tissue infection 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Staphylococcal bacteraemia 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Varicella 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Injury, poisoning and procedural complications
    Anaphylactic transfusion reaction 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Metabolism and nutrition disorders
    Dehydration 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypercreatininaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hyponatraemia 0/16 (0%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 2/16 (12.5%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Bone pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Pain in extremity 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Osteosarcoma 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Osteosarcoma metastatic 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Refractory anaemia with an excess of blasts 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Tumour pain 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Nervous system disorders
    Dizziness 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Headache 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Intracranial pressure increased 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Seizure 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Slow speech 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Somnolence 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Tremor 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Psychiatric disorders
    Restlessness 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Anuria 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Urinary retention 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Urinary tract obstruction 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Hypoxia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pleural effusion 2/16 (12.5%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Pneumonitis 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pneumothorax 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Pulmonary embolism 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Respiratory failure 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dermatitis bullous 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Erythema 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Skin exfoliation 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Vascular disorders
    Hypertension 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypotension 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Other (Not Including Serious) Adverse Events
    Phase 1: Nab-Paclitaxel 120 mg/m^2 Phase 1: Nab-Paclitaxel 150 mg/m^2 Phase 1: Nab-Paclitaxel 180 mg/m^2 Phase 1: Nab-Paclitaxel 210 mg/m^2 Phase 1: Nab-Paclitaxel 240 mg/m^2 Phase 1: Nab-Paclitaxel 270 mg/m^2 Phase 2: Nab-Paclitaxel 240 mg/m^2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/16 (100%) 8/8 (100%) 14/14 (100%) 11/11 (100%) 8/8 (100%) 7/7 (100%) 42/42 (100%)
    Blood and lymphatic system disorders
    Anaemia 8/16 (50%) 6/8 (75%) 6/14 (42.9%) 5/11 (45.5%) 6/8 (75%) 6/7 (85.7%) 27/42 (64.3%)
    Febrile neutropenia 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Leukopenia 6/16 (37.5%) 1/8 (12.5%) 2/14 (14.3%) 5/11 (45.5%) 5/8 (62.5%) 3/7 (42.9%) 18/42 (42.9%)
    Lymphadenitis 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Lymphopenia 6/16 (37.5%) 2/8 (25%) 1/14 (7.1%) 2/11 (18.2%) 2/8 (25%) 3/7 (42.9%) 5/42 (11.9%)
    Neutropenia 7/16 (43.8%) 4/8 (50%) 6/14 (42.9%) 8/11 (72.7%) 7/8 (87.5%) 6/7 (85.7%) 23/42 (54.8%)
    Neutrophilia 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Thrombocytopenia 1/16 (6.3%) 2/8 (25%) 2/14 (14.3%) 1/11 (9.1%) 2/8 (25%) 4/7 (57.1%) 8/42 (19%)
    Thrombocytosis 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Cardiac disorders
    Aortic valve disease 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Palpitations 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pericardial effusion 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Sinus bradycardia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Sinus tachycardia 0/16 (0%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Congenital, familial and genetic disorders
    Hydrocele 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Ear and labyrinth disorders
    Ear pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 3/42 (7.1%)
    Ear swelling 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Vertigo 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Endocrine disorders
    Cushingoid 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Eye disorders
    Diplopia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dry eye 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Eye irritation 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Eye pain 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Eye pruritus 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Keratitis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Lacrimation increased 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Periorbital oedema 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 2/11 (18.2%) 0/8 (0%) 1/7 (14.3%) 3/42 (7.1%)
    Photophobia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Vision blurred 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 5/42 (11.9%)
    Gastrointestinal disorders
    Abdominal distension 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Abdominal pain 2/16 (12.5%) 2/8 (25%) 3/14 (21.4%) 2/11 (18.2%) 3/8 (37.5%) 2/7 (28.6%) 6/42 (14.3%)
    Abdominal pain upper 0/16 (0%) 1/8 (12.5%) 2/14 (14.3%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Anal fissure 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Anal incontinence 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Anal inflammation 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Anorectal discomfort 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Ascites 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Constipation 4/16 (25%) 3/8 (37.5%) 3/14 (21.4%) 6/11 (54.5%) 2/8 (25%) 1/7 (14.3%) 10/42 (23.8%)
    Diarrhoea 2/16 (12.5%) 4/8 (50%) 4/14 (28.6%) 3/11 (27.3%) 4/8 (50%) 2/7 (28.6%) 8/42 (19%)
    Diarrhoea haemorrhagic 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Dyspepsia 0/16 (0%) 2/8 (25%) 1/14 (7.1%) 0/11 (0%) 2/8 (25%) 0/7 (0%) 2/42 (4.8%)
    Eructation 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Flatulence 0/16 (0%) 0/8 (0%) 2/14 (14.3%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Gastrointestinal pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Gastrooesophageal reflux disease 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Haematochezia 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Haemorrhoids 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Nausea 6/16 (37.5%) 3/8 (37.5%) 2/14 (14.3%) 4/11 (36.4%) 2/8 (25%) 3/7 (42.9%) 10/42 (23.8%)
    Odynophagia 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Salivary hypersecretion 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Stomatitis 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 2/11 (18.2%) 1/8 (12.5%) 2/7 (28.6%) 8/42 (19%)
    Toothache 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Vomiting 8/16 (50%) 3/8 (37.5%) 2/14 (14.3%) 3/11 (27.3%) 3/8 (37.5%) 1/7 (14.3%) 14/42 (33.3%)
    General disorders
    Asthenia 1/16 (6.3%) 1/8 (12.5%) 1/14 (7.1%) 1/11 (9.1%) 3/8 (37.5%) 1/7 (14.3%) 9/42 (21.4%)
    Catheter site pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Face oedema 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Fatigue 3/16 (18.8%) 3/8 (37.5%) 4/14 (28.6%) 4/11 (36.4%) 2/8 (25%) 0/7 (0%) 2/42 (4.8%)
    General physical health deterioration 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 1/11 (9.1%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Generalised oedema 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Influenza like illness 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Malaise 1/16 (6.3%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Non-cardiac chest pain 0/16 (0%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Oedema peripheral 3/16 (18.8%) 3/8 (37.5%) 2/14 (14.3%) 1/11 (9.1%) 1/8 (12.5%) 0/7 (0%) 8/42 (19%)
    Pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Pyrexia 6/16 (37.5%) 3/8 (37.5%) 5/14 (35.7%) 5/11 (45.5%) 4/8 (50%) 2/7 (28.6%) 14/42 (33.3%)
    Xerosis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Infections and infestations
    Bacillus bacteraemia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Cellulitis 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Clostridium difficile infection 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Conjunctivitis 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Cystitis 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Device related infection 0/16 (0%) 0/8 (0%) 2/14 (14.3%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Ear infection 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Herpes zoster 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Infection 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Lung infection 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Mucosal infection 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Oral candidiasis 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Oropharyngeal candidiasis 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Otitis externa 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Otitis media 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Paronychia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Rash pustular 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Rhinitis 0/16 (0%) 1/8 (12.5%) 2/14 (14.3%) 1/11 (9.1%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Skin infection 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 1/7 (14.3%) 0/42 (0%)
    Upper respiratory tract infection 2/16 (12.5%) 0/8 (0%) 1/14 (7.1%) 1/11 (9.1%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Urinary tract infection 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 2/42 (4.8%)
    Vulvitis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Injury, poisoning and procedural complications
    Arthropod bite 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Contusion 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Excoriation 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Fall 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 2/8 (25%) 0/7 (0%) 0/42 (0%)
    Humerus fracture 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Muscle injury 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Recall phenomenon 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Scar 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Vascular access complication 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Wound secretion 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Alanine aminotransferase increased 0/16 (0%) 3/8 (37.5%) 1/14 (7.1%) 3/11 (27.3%) 1/8 (12.5%) 1/7 (14.3%) 2/42 (4.8%)
    Aspartate aminotransferase increased 0/16 (0%) 2/8 (25%) 1/14 (7.1%) 1/11 (9.1%) 1/8 (12.5%) 0/7 (0%) 3/42 (7.1%)
    Blood alkaline phosphatase increased 0/16 (0%) 4/8 (50%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Blood bicarbonate decreased 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Blood bilirubin increased 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Blood creatinine increased 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Blood lactate dehydrogenase increased 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Blood urea increased 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    C-reactive protein increased 0/16 (0%) 0/8 (0%) 0/14 (0%) 2/11 (18.2%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Candida test positive 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Electrocardiogram QT prolonged 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Electroencephalogram abnormal 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Gamma-glutamyltransferase increased 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Glucose urine present 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    International normalised ratio increased 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Neutrophil count decreased 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 1/7 (14.3%) 1/42 (2.4%)
    Platelet count decreased 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Urine output decreased 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Weight decreased 2/16 (12.5%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 2/8 (25%) 2/7 (28.6%) 1/42 (2.4%)
    Weight increased 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Metabolism and nutrition disorders
    Acidosis 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Cachexia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Decreased appetite 3/16 (18.8%) 3/8 (37.5%) 5/14 (35.7%) 1/11 (9.1%) 1/8 (12.5%) 1/7 (14.3%) 6/42 (14.3%)
    Dehydration 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hyperchloraemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypercreatininaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hyperglycaemia 2/16 (12.5%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hyperkalaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypermagnesaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypernatraemia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hyperphosphataemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Hypertriglyceridaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypoalbuminaemia 2/16 (12.5%) 3/8 (37.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Hypocalcaemia 2/16 (12.5%) 2/8 (25%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Hypochloraemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypoglycaemia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypokalaemia 1/16 (6.3%) 3/8 (37.5%) 2/14 (14.3%) 1/11 (9.1%) 1/8 (12.5%) 2/7 (28.6%) 5/42 (11.9%)
    Hypomagnesaemia 1/16 (6.3%) 1/8 (12.5%) 1/14 (7.1%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Hyponatraemia 1/16 (6.3%) 4/8 (50%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Hypophosphataemia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Polydipsia 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/16 (6.3%) 2/8 (25%) 0/14 (0%) 4/11 (36.4%) 2/8 (25%) 2/7 (28.6%) 3/42 (7.1%)
    Back pain 2/16 (12.5%) 2/8 (25%) 3/14 (21.4%) 0/11 (0%) 2/8 (25%) 0/7 (0%) 1/42 (2.4%)
    Bone pain 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Coccydynia 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Epiphysiolysis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Flank pain 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Groin pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Joint swelling 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Muscular weakness 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Musculoskeletal chest pain 1/16 (6.3%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Musculoskeletal pain 2/16 (12.5%) 1/8 (12.5%) 1/14 (7.1%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Myalgia 0/16 (0%) 4/8 (50%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Neck pain 1/16 (6.3%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Pain in extremity 2/16 (12.5%) 3/8 (37.5%) 2/14 (14.3%) 0/11 (0%) 3/8 (37.5%) 1/7 (14.3%) 17/42 (40.5%)
    Pain in jaw 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Spinal pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 1/16 (6.3%) 0/8 (0%) 2/14 (14.3%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Skin papilloma 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Tumour haemorrhage 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Tumour pain 2/16 (12.5%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 3/42 (7.1%)
    Nervous system disorders
    Depressed level of consciousness 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dizziness 1/16 (6.3%) 2/8 (25%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Dysaesthesia 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Dysgeusia 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Headache 3/16 (18.8%) 2/8 (25%) 3/14 (21.4%) 2/11 (18.2%) 1/8 (12.5%) 1/7 (14.3%) 11/42 (26.2%)
    Lethargy 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Neuralgia 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 3/42 (7.1%)
    Neuropathy peripheral 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Paraesthesia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 1/7 (14.3%) 1/42 (2.4%)
    Peripheral motor neuropathy 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 2/8 (25%) 0/7 (0%) 0/42 (0%)
    Peripheral sensory neuropathy 1/16 (6.3%) 0/8 (0%) 2/14 (14.3%) 0/11 (0%) 3/8 (37.5%) 2/7 (28.6%) 3/42 (7.1%)
    Posterior reversible encephalopathy syndrome 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Sciatica 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Somnolence 1/16 (6.3%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Spinal cord compression 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Visual field defect 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Psychiatric disorders
    Anxiety 2/16 (12.5%) 3/8 (37.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Confusional state 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Depression 1/16 (6.3%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Enuresis 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Insomnia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 2/11 (18.2%) 0/8 (0%) 1/7 (14.3%) 2/42 (4.8%)
    Mood altered 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Restlessness 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dysuria 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Haematuria 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Ketonuria 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pollakiuria 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Polyuria 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Renal pain 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Urinary incontinence 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Urinary retention 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Urinary tract obstruction 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Urinary tract pain 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Reproductive system and breast disorders
    Genital pain 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Menstruation irregular 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Oedema genital 0/16 (0%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Scrotal oedema 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Vaginal haemorrhage 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Vulvovaginal discomfort 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Cough 2/16 (12.5%) 3/8 (37.5%) 2/14 (14.3%) 4/11 (36.4%) 3/8 (37.5%) 0/7 (0%) 6/42 (14.3%)
    Dysaesthesia pharynx 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dysphonia 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Dyspnoea 3/16 (18.8%) 0/8 (0%) 2/14 (14.3%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Epistaxis 1/16 (6.3%) 2/8 (25%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 2/7 (28.6%) 5/42 (11.9%)
    Haemoptysis 0/16 (0%) 1/8 (12.5%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Hypoxia 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Lung consolidation 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Nasal congestion 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Oropharyngeal pain 0/16 (0%) 2/8 (25%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Pharyngeal erythema 0/16 (0%) 2/8 (25%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Pharyngeal inflammation 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pleural effusion 2/16 (12.5%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Productive cough 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pulmonary haemorrhage 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Rhinitis allergic 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Tachypnoea 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Wheezing 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Skin and subcutaneous tissue disorders
    Alopecia 2/16 (12.5%) 4/8 (50%) 4/14 (28.6%) 5/11 (45.5%) 3/8 (37.5%) 2/7 (28.6%) 6/42 (14.3%)
    Dermatitis 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dermatitis acneiform 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dermatitis atopic 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Dry skin 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 2/11 (18.2%) 2/8 (25%) 2/7 (28.6%) 2/42 (4.8%)
    Ecchymosis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Erythema 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 2/11 (18.2%) 2/8 (25%) 1/7 (14.3%) 7/42 (16.7%)
    Haemorrhage subcutaneous 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Intertrigo 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Nail bed inflammation 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 0/42 (0%)
    Nail discolouration 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 1/7 (14.3%) 0/42 (0%)
    Onychoclasis 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Onycholysis 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Pain of skin 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 2/7 (28.6%) 0/42 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 2/42 (4.8%)
    Photosensitivity reaction 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 3/42 (7.1%)
    Pruritus 1/16 (6.3%) 2/8 (25%) 0/14 (0%) 1/11 (9.1%) 1/8 (12.5%) 1/7 (14.3%) 2/42 (4.8%)
    Pruritus generalised 3/16 (18.8%) 0/8 (0%) 1/14 (7.1%) 1/11 (9.1%) 0/8 (0%) 2/7 (28.6%) 5/42 (11.9%)
    Rash 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Rash erythematous 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 1/11 (9.1%) 0/8 (0%) 1/7 (14.3%) 1/42 (2.4%)
    Rash macular 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 1/8 (12.5%) 1/7 (14.3%) 0/42 (0%)
    Rash maculo-papular 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 2/8 (25%) 1/7 (14.3%) 7/42 (16.7%)
    Rash papular 0/16 (0%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 1/42 (2.4%)
    Skin exfoliation 0/16 (0%) 0/8 (0%) 1/14 (7.1%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 2/42 (4.8%)
    Skin hyperpigmentation 0/16 (0%) 1/8 (12.5%) 0/14 (0%) 1/11 (9.1%) 2/8 (25%) 0/7 (0%) 1/42 (2.4%)
    Toxic erythema of chemotherapy 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 1/7 (14.3%) 0/42 (0%)
    Vascular disorders
    Hyperaemia 0/16 (0%) 0/8 (0%) 0/14 (0%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 3/42 (7.1%)
    Hypertension 1/16 (6.3%) 1/8 (12.5%) 0/14 (0%) 0/11 (0%) 1/8 (12.5%) 0/7 (0%) 1/42 (2.4%)
    Hypotension 0/16 (0%) 1/8 (12.5%) 2/14 (14.3%) 0/11 (0%) 0/8 (0%) 0/7 (0%) 0/42 (0%)
    Lymphoedema 1/16 (6.3%) 0/8 (0%) 0/14 (0%) 1/11 (9.1%) 0/8 (0%) 0/7 (0%) 0/42 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results from a center cannot be submitted for publication before results of multicenter study are published unless it is more than one year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to ninety days. Investigator must delete confidential information before submission or defer publication to permit patent applications

    Results Point of Contact

    Name/Title Anne McClain, Senior Manager
    Organization Celgene Corporation
    Phone 888-260-1599
    Email ClinicalTrialDisclosure@Celgene.com
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT01962103
    Other Study ID Numbers:
    • ABI-007-PST-001
    First Posted:
    Oct 14, 2013
    Last Update Posted:
    Dec 27, 2019
    Last Verified:
    Dec 1, 2019