Clincosm LogoSign in Get a demo

MPACT Study to Compare Effects of Targeted Drugs on Tumor Gene Variations

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01827384
Collaborator
(none)
208
Enrollment
8
Locations
4
Arms
93.2
Actual Duration (Months)
26
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies molecular profiling-based assignment of cancer therapy (MPACT) in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Adavosertib, everolimus, and trametinib are drugs that each target a specific variation in tumors by blocking different proteins needed for cell growth. Veliparib blocks an enzyme that helps repair deoxyribonucleic acid (DNA) damaged by chemotherapy, which may help chemotherapy drugs work better. It is not yet known whether testing patients for variations in their tumor and assigning treatment targeting the variation is more effective than standard non-targeted therapy in treating advanced solid tumors.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

PRIMARY OBJECTIVE:
  1. Evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers.

OUTLINE: Patients are assigned to 1 of 4 treatment regimens corresponding to one of their mutation/amplification categories.

REGIMEN I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7 and temozolomide PO once daily (QD) on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

REGIMEN II: Patients receive adavosertib PO BID for 5 doses starting on day 1 and carboplatin intravenously (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. (No longer an active study drug as of March 2018)

REGIMEN III: Patients receive everolimus PO every day (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (No longer an active study drug as of March 2018)

REGIMEN IV: Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (No longer an active study drug as of March 2018)

After completion of study treatment, patients are followed up for 30 days. Patients with unacceptable toxicities that have not resolved by day 30 are followed up biweekly until stabilization or resolution.

Study Design

Study Type:
Interventional
Actual Enrollment :
208 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Molecular Profiling-Based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors
Actual Study Start Date :
Dec 31, 2013
Actual Primary Completion Date :
Jun 19, 2021
Actual Study Completion Date :
Oct 8, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Regimen I (veliparib, temozolomide)

Patients receive veliparib by mouth (PO) twice a day (BID) on days 1-7 and temozolomide PO every day (QD) on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Temozolomide
Given by mouth (PO)
Other Names:
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Methazolastone
  • RP-46161
  • SCH 52365
  • Temcad
  • Temodal
  • Temodar
  • Temomedac
  • TMZ

    • Drug: Veliparib
    Given by mouth (PO)
    Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888

    		•
    Experimental: Regimen II (adavosertib, carboplatin)

    Patients receive adavosertib by mouth (PO) twice a day (BID) for 5 doses starting on day 1 and carboplatin intravenous (IV) over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Drug: Adavosertib
    Given by mouth (PO)
    Other Names:
  • AZD-1775
  • AZD1775
  • MK-1775
  • MK1775

    • Drug: Carboplatin
    Given intravenous (IV)
    Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carboplatinum
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo

    		•
    Experimental: Regimen III (everolimus)

    Patients receive everolimus by mouth (PO) every day (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Everolimus
    Given by mouth (PO)
    Other Names:
  • 42-O-(2-Hydroxy)ethyl Rapamycin
  • Afinitor
  • Certican
  • RAD 001
  • RAD001
  • Votubia
  • Zortress

    		•
    Experimental: Regimen IV (trametinib)

    Patients receive trametinib by mouth (PO) every day (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Trametinib
    Given by mouth (PO)
    Other Names:
  • GSK1120212
  • JTP-74057
  • MEK Inhibitor GSK1120212

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With an Objective Response [Up to 30 days after completion of study treatment, up to 75 months]

      ORR is the proportion of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all tumors. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

    Secondary Outcome Measures

    1. Proportion of Participants With 4 Month Progression-free Survival (PFS) [4 months]

      Time from random assignment to progression or death from any cause (whichever comes first). Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions is also considered progressions.

    Other Outcome Measures

    1. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) [Date treatment consent signed to date off study, approx. 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.]

      Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • TUMOR BIOPSY SEQUENCING: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy and/or no standard of treatment exists that has been shown to prolong survival

    • TUMOR BIOPSY SEQUENCING: Patient must have tumor amenable to percutaneous or excisional skin biopsy and be willing to undergo a tumor biopsy or biopsy samples (formalin-fixed paraffin-embedded [FFPE] blocks) collected on another study or from a procedure performed due to medical necessity may be acceptable if collected within 6 months prior to registration on molecular profiling-based assignment of cancer therapy (MPACT) and providing that the patient has not received any investigational or targeted treatment since that time, or a report from a Molecular Analysis for Therapy Choice (MATCH) study designated Clinical Laboratory Improvement Act (CLIA) laboratory that a patient has a variant in the genes of interest

    • TUMOR BIOPSY SEQUENCING: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan

    • TUMOR BIOPSY SEQUENCING: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment; patients with prostate cancer may continue luteinizing hormone-releasing hormone (LHRH) agonists or antagonists

    • TUMOR BIOPSY SEQUENCING: Karnofsky performance status >= 70%

    • TUMOR BIOPSY SEQUENCING: Life expectancy > 3 months

    • TUMOR BIOPSY SEQUENCING: Absolute neutrophil count >= 1,000/uL (mcL)

    • TUMOR BIOPSY SEQUENCING: Platelets >= 100,000/uL (mcL)

    • TUMOR BIOPSY SEQUENCING: Total bilirubin < 1.5 x institutional upper limit of normal

    • TUMOR BIOPSY SEQUENCING: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal

    • TUMOR BIOPSY SEQUENCING: Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels >= 1.5 x institutional upper limit of normal

    • TUMOR BIOPSY SEQUENCING: The effects of these targeted agents on the developing human fetus are unknown or anticipated to cause fetal harm based on their mechanism of action; for this reason, women of childbearing potential and men must agree to use highly effective contraception prior to study entry, for the duration of study participation, and for 3 months after completion of study; because there may be a risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the patient is on this trial and for 30 days following last dose of study drug

    • TUMOR BIOPSY SEQUENCING: Patients with history of central nervous system (CNS) metastases who have received treatment and who either have not had seizures or have been on stable doses of anti-seizure medicine and had no seizures for 4 weeks will be eligible; enzyme-inducing anticonvulsants are contraindicated

    • TUMOR BIOPSY SEQUENCING: Ability to understand and the willingness to sign a written informed consent document (subjects with impaired decision-making capacity are not eligible)

    • TREATMENT: Patient must have predefined targeted mutation in tumor biopsy

    • TREATMENT: Patients with histologically documented solid tumors whose disease has progressed following at least one line of standard therapy or for which no standard therapy exists that has been shown to prolong survival

    • TREATMENT: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan

    • TREATMENT: Any prior therapy, radiotherapy, or major surgery must have been completed

    = 3 weeks (> 6 weeks for nitrosoureas or mitomycin C) or 5 half-lives of the agent (whichever is shorter) prior to enrollment on protocol, and the participant must have recovered to eligibility levels from prior toxicity; radiofrequency ablation (RFA) of localized lesions should have been performed >= 2 weeks prior to treatment

    • TREATMENT: Patients with bone metastases or hypercalcemia on intravenous bisphosphonate treatment, denosumab, or similar agents are eligible to participate and may continue this treatment; patients with prostate cancer may continue LHRH agonists or antagonists

    • TREATMENT: Karnofsky performance status >= 70%

    • TREATMENT: Absolute neutrophil count >= 1,000/uL (mcL)

    • TREATMENT: Platelets >= 100,000/uL (mcL)

    • TREATMENT: Total bilirubin < 1.5 x institutional upper limit of normal

    • TREATMENT: AST (SGOT)/ALT (SGPT) =< 3 x institutional upper limit of normal

    • TREATMENT: Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels >= 1.5 x institutional upper limit of normal

    • TREATMENT: Life expectancy > 3 months

    • TREATMENT: The effects of these targeted agents on the developing human fetus are unknown or anticipated to cause fetal harm based on their mechanism of action; for this reason, women of childbearing potential and men must agree to use highly effective contraception (see list below) prior to study entry, for the duration of study participation, and for 3 months after completion of study;

    • Total abstinence: When this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)

    • Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment

    • In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment

    • Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female subjects on the study, the vasectomized male partner should be the sole partner for that subject); use of a combination of any two of the following:

    • Use of oral, injected, implanted or other hormonal methods of contraception

    • Placement of an intrauterine device (IUD) or intrauterine system (IUS)

    • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

    • In case of use of oral contraception, women should have been stable on the oral agent before taking study treatment

    • Sexually active males must use a condom during intercourse

    • TREATMENT: Because there may be a risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued while the patient is on this trial and for 30 days following last dose of study drug

    • TREATMENT: Patients with ovarian cancer or metastatic breast cancer and breast cancer gene (BRCA) mutations must have received approved poly (ADP-ribose) polymerase (PARP) inhibitor therapy; these patients are eligible for the veliparib plus temozolomide arm unless the PARP inhibitor was administered with temozolomide

    • TREATMENT: Patients with a history of seizures are not eligible to receive veliparib

    • TREATMENT: Patients who have had prior treatment with any PARP inhibitor in combination with temozolomide are not eligible to receive treatment with veliparib on this study; patients who have received prior temozolomide or PARP inhibitor with or without other chemotherapy/targeted agent should not be excluded

    • TREATMENT: Patients must have >= 10.0 g/dL hemoglobin (Hb) and no blood transfusion in the past 28 days to receive veliparib

    Exclusion Criteria:

    • TUMOR BIOPSY SEQUENCING: Women who are pregnant or breastfeeding

    • TUMOR BIOPSY SEQUENCING: Patients who are receiving any other investigational agents; patients on other trials will be eligible as long as they are no longer receiving study treatment

    • TUMOR BIOPSY SEQUENCING: Patients with uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the past 6 months, invasive fungal infections, or active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e., quantifiable hepatitis B virus [HBV]-DNA and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA]) are not eligible to participate; testing for hepatitis B or other infections for eligibility will be performed only if clinically indicated

    • TUMOR BIOPSY SEQUENCING: Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with Crohn's disease or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow tablets or capsules whole; tablets or capsules must not be crushed or chewed; nasogastric or gastrostomy tube (G-tube) administration is not allowed

    • TUMOR BIOPSY SEQUENCING: Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic (PK) interactions

    • TUMOR BIOPSY SEQUENCING: Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use

    • TUMOR BIOPSY SEQUENCING: Patients who have previously been treated with the combination of temozolomide plus a PARP inhibitor should not be considered eligible for a biopsy given that these patients would not be eligible for the active veliparib plus temozolomide arm

    • TREATMENT: Women who are pregnant or breastfeeding

    • TREATMENT: Patients who are receiving any other investigational agents; patients on other trials will be eligible as long as they are no longer receiving study treatment

    • TREATMENT: Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial; patients who have a history of seizures are not eligible to receive veliparib

    • TREATMENT: Patients with uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, myocardial infarction in the past 6 months, invasive fungal infections, or active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e., quantifiable hepatitis B virus (HBV)-DNA and/or positive hepatitis B surface antibody (HbsAg), quantifiable hepatitis C virus (HCV)-RNA) are not eligible to participate; testing for hepatitis B or other infections for eligibility will be performed only if clinically indicated

    • TREATMENT: Patients with gastrointestinal conditions that might predispose for drug intolerability or poor drug absorption (e.g., inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with Crohn's disease or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow tablets or capsules whole; tablets or capsules must not be crushed or chewed; nasogastric or G-tube administration is not allowed

    • TREATMENT: HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for PK interactions

    • TREATMENT: Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics (i.e., cytochrome P450, family 3, subfamily A, polypeptide 4 [CYP450], P-glycoprotein [PgP]) of any of the study drugs will be determined following review of their cases by the principal investigator (PI); patients on strong and moderate cytochrome P450 system inducers or inhibitors are ineligible; every effort would be made to switch patients off medications that are known substrates of CYP450; if it is medically important for the patient to remain on such medications, these patients can still be eligible to participate based on PI discretion

    • TREATMENT: Patients who require use of coumarin-derivative anticoagulants such as warfarin are excluded; low molecular weight heparin is permitted for prophylactic or therapeutic use

    • TREATMENT: Patients who have a history of another primary malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for > 3 years

    • TREATMENT: Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic syndrome (MDS), or with features suggestive of AML/MDS, or who have had prior allogeneic bone marrow transplant or double umbilical cord blood transplantation, should not receive veliparib due to reports of MDS and leukemia secondary to oncology therapy on Cancer Therapy Evaluation Program (CTEP)-sponsored studies utilizing veliparib

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Colorado Hospital Aurora Colorado United States 80045
    2 Emory University Hospital/Winship Cancer Institute Atlanta Georgia United States 30322
    3 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
    4 National Cancer Institute Developmental Therapeutics Clinic Bethesda Maryland United States 20892
    5 Washington University School of Medicine Saint Louis Missouri United States 63110
    6 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08903
    7 University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania United States 15232
    8 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: A P Chen, National Cancer Institute LAO

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01827384
    Other Study ID Numbers:
    • NCI-2013-01588
    • NCI-2013-01588
    • MPACT
    • 130105
    • P121047
    • 9149
    • 9149
    • ZIABC011078
    First Posted:
    Apr 9, 2013
    Last Update Posted:
    May 10, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Carboplatin
    Everolimus
    Temozolomide
    Trametinib
    Veliparib
    Adavosertib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
    Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated.
    Period Title: Overall Study
    STARTED 13 1 9 1 1 22 2 1 2 15 7 1 2 131
    COMPLETED 13 1 9 1 1 22 2 1 2 15 7 1 2 0
    NOT COMPLETED 0 0 0 0 0 0 0 0 0 0 0 0 0 131

    Baseline Characteristics

    Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated Total
    Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated. Total of all reporting groups
    Overall Participants 13 1 9 1 1 22 2 1 2 15 7 1 2 131 208
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    46.2%
    1
    100%
    6
    66.7%
    1
    100%
    1
    100%
    13
    59.1%
    2
    100%
    1
    100%
    2
    100%
    11
    73.3%
    3
    42.9%
    1
    100%
    2
    100%
    89
    67.9%
    139
    66.8%
    >=65 years
    7
    53.8%
    0
    0%
    3
    33.3%
    0
    0%
    0
    0%
    9
    40.9%
    0
    0%
    0
    0%
    0
    0%
    4
    26.7%
    4
    57.1%
    0
    0%
    0
    0%
    42
    32.1%
    69
    33.2%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    61
    (15.15)
    59
    (0)
    54
    (15.15)
    59.1
    (0)
    59
    (0)
    58
    (12.22)
    54
    (9.9)
    45
    (0)
    55.95
    (7)
    59
    (10.54)
    63.2
    (13.72)
    39
    (0)
    61.65
    (4.03)
    58
    (11.53)
    57.75
    (11.51)
    Sex: Female, Male (Count of Participants)
    Female
    9
    69.2%
    0
    0%
    6
    66.7%
    1
    100%
    1
    100%
    12
    54.5%
    1
    50%
    0
    0%
    2
    100%
    13
    86.7%
    3
    42.9%
    1
    100%
    0
    0%
    67
    51.1%
    116
    55.8%
    Male
    4
    30.8%
    1
    100%
    3
    33.3%
    0
    0%
    0
    0%
    10
    45.5%
    1
    50%
    1
    100%
    0
    0%
    2
    13.3%
    4
    57.1%
    0
    0%
    2
    100%
    64
    48.9%
    92
    44.2%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    2
    9.1%
    0
    0%
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    0
    0%
    0
    0%
    11
    8.4%
    15
    7.2%
    Not Hispanic or Latino
    13
    100%
    1
    100%
    8
    88.9%
    1
    100%
    1
    100%
    19
    86.4%
    2
    100%
    1
    100%
    2
    100%
    14
    93.3%
    7
    100%
    1
    100%
    2
    100%
    117
    89.3%
    189
    90.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    2.3%
    4
    1.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.8%
    1
    0.5%
    Asian
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    0
    0%
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    0
    0%
    9
    6.9%
    13
    6.3%
    Native Hawaiian or Other Pacific Islander
    1
    7.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.5%
    Black or African American
    1
    7.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    4
    18.2%
    0
    0%
    0
    0%
    0
    0%
    2
    13.3%
    2
    28.6%
    0
    0%
    0
    0%
    19
    14.5%
    28
    13.5%
    White
    11
    84.6%
    1
    100%
    8
    88.9%
    1
    100%
    1
    100%
    15
    68.2%
    2
    100%
    1
    100%
    2
    100%
    9
    60%
    5
    71.4%
    1
    100%
    2
    100%
    95
    72.5%
    154
    74%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.1%
    0
    0%
    0
    0%
    0
    0%
    2
    13.3%
    0
    0%
    0
    0%
    0
    0%
    7
    5.3%
    11
    5.3%
    Region of Enrollment (participants) [Number]
    United States
    13
    100%
    1
    100%
    9
    100%
    1
    100%
    1
    100%
    22
    100%
    2
    100%
    1
    100%
    2
    100%
    15
    100%
    7
    100%
    1
    100%
    2
    100%
    131
    100%
    208
    100%
    Karnofsky Performance Status (Count of Participants)
    100
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    9.1%
    0
    0%
    0
    0%
    1
    50%
    1
    6.7%
    1
    14.3%
    0
    0%
    0
    0%
    6
    4.6%
    11
    5.3%
    90
    8
    61.5%
    1
    100%
    2
    22.2%
    1
    100%
    1
    100%
    14
    63.6%
    2
    100%
    0
    0%
    0
    0%
    8
    53.3%
    4
    57.1%
    1
    100%
    1
    50%
    76
    58%
    119
    57.2%
    80
    3
    23.1%
    0
    0%
    6
    66.7%
    0
    0%
    0
    0%
    6
    27.3%
    0
    0%
    1
    100%
    1
    50%
    6
    40%
    2
    28.6%
    0
    0%
    1
    50%
    41
    31.3%
    67
    32.2%
    70
    2
    15.4%
    0
    0%
    1
    11.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8
    6.1%
    11
    5.3%
    Participants with an Actionable Mutation of Interest (aMOI) in a Targeted Pathway (Count of Participants)
    Deoxyribonucleic acid (DNA) repair
    9
    69.2%
    1
    100%
    5
    55.6%
    0
    0%
    0
    0%
    4
    18.2%
    1
    50%
    1
    100%
    1
    50%
    11
    73.3%
    7
    100%
    0
    0%
    1
    50%
    21
    16%
    62
    29.8%
    P13K
    1
    7.7%
    0
    0%
    4
    44.4%
    0
    0%
    1
    100%
    1
    4.5%
    0
    0%
    0
    0%
    0
    0%
    3
    20%
    0
    0%
    1
    100%
    0
    0%
    4
    3.1%
    15
    7.2%
    RAS/RAF/MEK
    3
    23.1%
    0
    0%
    0
    0%
    1
    100%
    0
    0%
    17
    77.3%
    1
    50%
    0
    0%
    1
    50%
    1
    6.7%
    0
    0%
    0
    0%
    1
    50%
    13
    9.9%
    38
    18.3%
    No aMOI detected
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    93
    71%
    93
    44.7%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With an Objective Response
    Description ORR is the proportion of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all tumors. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
    Time Frame Up to 30 days after completion of study treatment, up to 75 months

    Outcome Measure Data

    Analysis Population Description
    Participants enrolled but not treated were not applicable for this outcome measure.
    Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3
    Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD)
    Measure Participants 13 1 9 1 1 22 2 1 2 15 7 1 2
    Complete Response
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Partial Response
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    4.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Proportion of Participants With 4 Month Progression-free Survival (PFS)
    Description Time from random assignment to progression or death from any cause (whichever comes first). Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions is also considered progressions.
    Time Frame 4 months

    Outcome Measure Data

    Analysis Population Description
    Participants enrolled but not treated were not applicable for this outcome measure.
    Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3
    Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD)
    Measure Participants 13 1 9 1 1 22 2 1 2 15 7 1 2
    Number [proportion of participants]
    0.23
    1.8%
    0.00
    0%
    0.22
    2.4%
    0.00
    0%
    1.00
    100%
    0.41
    1.9%
    0.50
    25%
    0.00
    0%
    0.00
    0%
    0.13
    0.9%
    0.29
    4.1%
    0.00
    0%
    0.00
    0%
    3. Other Pre-specified Outcome
    Title Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
    Description Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
    Time Frame Date treatment consent signed to date off study, approx. 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.

    Outcome Measure Data

    Analysis Population Description
    Adverse events were collected for participants that were enrolled but not treated.
    Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
    Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated.
    Measure Participants 13 1 9 1 1 22 2 1 2 15 7 1 2 131
    Count of Participants [Participants]
    13
    100%
    1
    100%
    9
    100%
    1
    100%
    1
    100%
    22
    100%
    2
    100%
    1
    100%
    2
    100%
    15
    100%
    7
    100%
    1
    100%
    2
    100%
    2
    1.5%

    Adverse Events

    Time Frame Date treatment consent signed to date off study, approximately 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.
    Adverse Event Reporting Description
    Arm/Group Title Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
    Arm/Group Description TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC1: Veliparib (ABT-888) 40mg by mouth (PO) twice a day (BID) on days 1-7; Temozolomide 150 mg/m^2 PO every day (QD) on days 1-5 TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC2: Everolimus 10 mg by mouth (PO) every day (QD) TAC4: Adavosertib (MK-1775) 225 mg by mouth (PO) twice a day (BID) x 5 doses on days 1-3; Carboplatin area under the concentration (AUC) 5 intravenous (IV) over 30 min on day 1 TAC3: Trametinib 2mg by mouth (PO) every day (QD) Participants who signed consent and were enrolled but not treated.
    All Cause Mortality
    Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
    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 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 1/13 (7.7%) 0/1 (0%) 3/9 (33.3%) 0/1 (0%) 0/1 (0%) 1/22 (4.5%) 0/2 (0%) 0/1 (0%) 0/2 (0%) 1/15 (6.7%) 1/7 (14.3%) 0/1 (0%) 0/2 (0%) 5/131 (3.8%)
    Serious Adverse Events
    Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
    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 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 5/13 (38.5%) 0/1 (0%) 4/9 (44.4%) 1/1 (100%) 0/1 (0%) 11/22 (50%) 1/2 (50%) 1/1 (100%) 1/2 (50%) 10/15 (66.7%) 4/7 (57.1%) 1/1 (100%) 2/2 (100%) 10/131 (7.6%)
    Blood and lymphatic system disorders
    Anemia 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 2/15 (13.3%) 3 1/7 (14.3%) 2 1/1 (100%) 1 1/2 (50%) 2 0/131 (0%) 0
    Febrile neutropenia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 3/15 (20%) 3 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/13 (7.7%) 2 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/131 (0.8%) 1
    Ascites 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Colitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Colonic obstruction 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Colonic perforation 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Constipation 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Diarrhea 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 2/15 (13.3%) 2 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Ileus 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Nausea 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Rectal hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Small intestinal obstruction 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Small intestinal perforation 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vomiting 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 2 1/1 (100%) 1 0/2 (0%) 0 3/15 (20%) 3 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders
    Death NOS 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Edema limbs 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Fever 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Infusion related reaction 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Sudden death NOS 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Infections and infestations
    Bronchial infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Lung infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Sepsis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 1/1 (100%) 1 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 2/131 (1.5%) 3
    Urinary tract infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 2 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Injury, poisoning and procedural complications
    Hip fracture 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 2 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Postoperative hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Investigations
    Alanine aminotransferase increased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Alkaline phosphatase increased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Aspartate aminotransferase increased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 2/131 (1.5%) 2
    Blood bilirubin increased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Neutrophil count decreased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 1/15 (6.7%) 1 2/7 (28.6%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Platelet count decreased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 3/15 (20%) 3 0/7 (0%) 0 1/1 (100%) 1 1/2 (50%) 2 0/131 (0%) 0
    White blood cell decreased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 2 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hyperkalemia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Hypoglycemia 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypokalemia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypomagnesemia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Hyponatremia 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 1/2 (50%) 1 1/131 (0.8%) 1
    Hypophosphatemia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Muscle weakness right-sided 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, CNS Metastasis 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Progressive disease 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Nervous system disorders
    Dizziness 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Presyncope 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Syncope 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Renal and urinary disorders - Other, Urinary tract obstruction 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Renal and urinary disorders - Other, ureter obstruction 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Urinary tract obstruction 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Dyspnea 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 2/131 (1.5%) 2
    Hypoxia 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Laryngeal hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Pleural effusion 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Pneumothorax 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Respiratory, thoracic and mediastinal disorders - Other, Shortness of breath 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vascular disorders
    Hypertension 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 2 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypotension 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/131 (0.8%) 1
    Thromboembolic event 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Other (Not Including Serious) Adverse Events
    Treatment Assignment Code 1 (TAC1) TAC1 -> TAC4 TAC2 TAC2 -> TAC1 TAC2 -> TAC3 TAC3 TAC3 -> TAC1 TAC3 -> TAC1 -> TAC4 TAC3 -> TAC4 TAC4 TAC4 -> TAC1 TAC4 -> TAC2 TAC4 -> TAC3 Participants Enrolled But Not Treated
    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 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 13/13 (100%) 1/1 (100%) 9/9 (100%) 1/1 (100%) 1/1 (100%) 22/22 (100%) 2/2 (100%) 1/1 (100%) 2/2 (100%) 15/15 (100%) 7/7 (100%) 1/1 (100%) 2/2 (100%) 2/131 (1.5%)
    Blood and lymphatic system disorders
    Anemia 5/13 (38.5%) 13 0/1 (0%) 0 3/9 (33.3%) 7 1/1 (100%) 3 0/1 (0%) 0 9/22 (40.9%) 26 1/2 (50%) 3 1/1 (100%) 1 1/2 (50%) 6 10/15 (66.7%) 23 6/7 (85.7%) 27 1/1 (100%) 3 2/2 (100%) 9 2/131 (1.5%) 5
    Hemolysis 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Thrombotic thrombocytopenic purpura 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Electrocardiogram QT corrected interval prolonged 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Palpitations 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Sinus bradycardia 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 4 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Sinus tachycardia 3/13 (23.1%) 5 0/1 (0%) 0 1/9 (11.1%) 1 1/1 (100%) 2 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 1/1 (100%) 1 0/2 (0%) 0 1/131 (0.8%) 1
    Endocrine disorders
    Hypothyroidism 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Eye disorders
    Conjunctivitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Corneal ulcer 0/13 (0%) 0 1/1 (100%) 2 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Dry eye 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Eye disorders - Other, Blepharitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Eye disorders - Other, Peripheral shadow 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Glaucoma 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Watering eyes 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Abdominal pain 4/13 (30.8%) 5 1/1 (100%) 3 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 4 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 1/2 (50%) 1 1/131 (0.8%) 2
    Ascites 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 1/1 (100%) 1 1/2 (50%) 1 0/131 (0%) 0
    Bloating 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Cheilitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Constipation 7/13 (53.8%) 8 1/1 (100%) 2 4/9 (44.4%) 4 1/1 (100%) 1 0/1 (0%) 0 6/22 (27.3%) 7 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 3/15 (20%) 3 5/7 (71.4%) 5 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Diarrhea 4/13 (30.8%) 4 1/1 (100%) 4 2/9 (22.2%) 2 0/1 (0%) 0 1/1 (100%) 1 11/22 (50%) 16 2/2 (100%) 4 1/1 (100%) 1 2/2 (100%) 4 7/15 (46.7%) 10 6/7 (85.7%) 10 1/1 (100%) 1 1/2 (50%) 2 0/131 (0%) 0
    Dry mouth 0/13 (0%) 0 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Dyspepsia 1/13 (7.7%) 1 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 3/7 (42.9%) 4 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Gastroesophageal reflux disease 2/13 (15.4%) 2 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Gastrointestinal pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Lower gastrointestinal hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Mucositis oral 1/13 (7.7%) 1 0/1 (0%) 0 3/9 (33.3%) 4 0/1 (0%) 0 1/1 (100%) 2 2/22 (9.1%) 3 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Nausea 9/13 (69.2%) 14 0/1 (0%) 0 4/9 (44.4%) 4 1/1 (100%) 1 1/1 (100%) 1 11/22 (50%) 14 0/2 (0%) 0 1/1 (100%) 1 2/2 (100%) 3 11/15 (73.3%) 20 5/7 (71.4%) 10 0/1 (0%) 0 2/2 (100%) 2 1/131 (0.8%) 1
    Rectal hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vomiting 8/13 (61.5%) 15 0/1 (0%) 0 3/9 (33.3%) 3 0/1 (0%) 0 1/1 (100%) 1 6/22 (27.3%) 11 1/2 (50%) 1 1/1 (100%) 1 2/2 (100%) 3 8/15 (53.3%) 9 4/7 (57.1%) 10 1/1 (100%) 1 0/2 (0%) 0 1/131 (0.8%) 1
    General disorders
    Chills 1/13 (7.7%) 1 1/1 (100%) 1 3/9 (33.3%) 4 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 5 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Edema limbs 1/13 (7.7%) 2 0/1 (0%) 0 4/9 (44.4%) 6 1/1 (100%) 1 0/1 (0%) 0 7/22 (31.8%) 12 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 2/7 (28.6%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Edema trunk 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Fatigue 8/13 (61.5%) 11 1/1 (100%) 4 4/9 (44.4%) 4 0/1 (0%) 0 1/1 (100%) 1 10/22 (45.5%) 16 1/2 (50%) 1 1/1 (100%) 2 2/2 (100%) 4 9/15 (60%) 12 4/7 (57.1%) 4 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Fever 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 4 0/2 (0%) 0 1/1 (100%) 1 1/2 (50%) 2 2/15 (13.3%) 3 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Flu like symptoms 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, Edema Limbs 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, GERD 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, Hand and Foot Syndrome 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, cellulitis 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, cellulitits 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, cellutitis 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, neutrophilic dermatoses 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    General disorders and administration site conditions - Other, neutrophilic dermatosis 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Infusion related reaction 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 2/15 (13.3%) 2 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Localized edema 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Malaise 1/13 (7.7%) 2 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Pain 3/13 (23.1%) 3 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 3/22 (13.6%) 3 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 2 1/131 (0.8%) 1
    Pain in extremity 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 2/15 (13.3%) 2 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Infections and infestations
    Infections and infestations - Other, urinary tract infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Paronychia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 2 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Sinusitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin infection 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Upper respiratory infection 0/13 (0%) 0 1/1 (100%) 1 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Urinary tract infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 2/15 (13.3%) 2 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vaginal infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vulval infection 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 2 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Injury, poisoning and procedural complications
    Bruising 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Fall 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Fracture 2/13 (15.4%) 2 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hip fracture 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 2/22 (9.1%) 3 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 1/7 (14.3%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Alanine aminotransferase increased 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 1/1 (100%) 3 0/1 (0%) 0 9/22 (40.9%) 15 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 2 2/15 (13.3%) 2 1/7 (14.3%) 1 1/1 (100%) 1 1/2 (50%) 1 1/131 (0.8%) 3
    Alkaline phosphatase increased 2/13 (15.4%) 2 0/1 (0%) 0 2/9 (22.2%) 4 0/1 (0%) 0 0/1 (0%) 0 6/22 (27.3%) 8 1/2 (50%) 2 0/1 (0%) 0 2/2 (100%) 2 4/15 (26.7%) 5 2/7 (28.6%) 4 1/1 (100%) 1 0/2 (0%) 0 1/131 (0.8%) 1
    Aspartate aminotransferase increased 2/13 (15.4%) 3 0/1 (0%) 0 3/9 (33.3%) 3 1/1 (100%) 2 0/1 (0%) 0 9/22 (40.9%) 20 1/2 (50%) 3 0/1 (0%) 0 1/2 (50%) 2 3/15 (20%) 4 4/7 (57.1%) 7 1/1 (100%) 1 2/2 (100%) 4 1/131 (0.8%) 3
    Blood bilirubin increased 1/13 (7.7%) 1 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 1/15 (6.7%) 8 1/7 (14.3%) 1 0/1 (0%) 0 1/2 (50%) 3 0/131 (0%) 0
    Cholesterol high 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Creatinine increased 3/13 (23.1%) 4 0/1 (0%) 0 2/9 (22.2%) 3 1/1 (100%) 1 0/1 (0%) 0 4/22 (18.2%) 11 1/2 (50%) 2 1/1 (100%) 4 1/2 (50%) 1 2/15 (13.3%) 3 4/7 (57.1%) 13 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    INR increased 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Investigations - Other, TSH Inc 2/13 (15.4%) 2 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Lymphocyte count decreased 6/13 (46.2%) 11 0/1 (0%) 0 4/9 (44.4%) 7 1/1 (100%) 4 0/1 (0%) 0 4/22 (18.2%) 7 1/2 (50%) 3 0/1 (0%) 0 1/2 (50%) 7 3/15 (20%) 5 3/7 (42.9%) 6 1/1 (100%) 5 1/2 (50%) 10 1/131 (0.8%) 1
    Lymphocyte count increased 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Neutrophil count decreased 2/13 (15.4%) 3 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 7/15 (46.7%) 10 3/7 (42.9%) 10 1/1 (100%) 3 1/2 (50%) 2 0/131 (0%) 0
    Platelet count decreased 8/13 (61.5%) 11 0/1 (0%) 0 3/9 (33.3%) 3 1/1 (100%) 2 0/1 (0%) 0 5/22 (22.7%) 12 1/2 (50%) 2 0/1 (0%) 0 1/2 (50%) 2 11/15 (73.3%) 25 7/7 (100%) 22 1/1 (100%) 7 2/2 (100%) 9 1/131 (0.8%) 1
    Weight gain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 2 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Weight loss 1/13 (7.7%) 2 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 2/7 (28.6%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    White blood cell decreased 3/13 (23.1%) 7 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 4 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 7/15 (46.7%) 15 3/7 (42.9%) 8 1/1 (100%) 4 1/2 (50%) 5 0/131 (0%) 0
    Metabolism and nutrition disorders
    Acidosis 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Anorexia 5/13 (38.5%) 6 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 5/15 (33.3%) 6 3/7 (42.9%) 3 0/1 (0%) 0 2/2 (100%) 2 0/131 (0%) 0
    Dehydration 2/13 (15.4%) 2 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 2/15 (13.3%) 2 2/7 (28.6%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypercalcemia 2/13 (15.4%) 2 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 6 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 5/7 (71.4%) 6 1/1 (100%) 2 0/2 (0%) 0 0/131 (0%) 0
    Hyperglycemia 2/13 (15.4%) 3 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hyperkalemia 1/13 (7.7%) 4 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 14 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 2/7 (28.6%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypermagnesemia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypernatremia 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 4 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 2 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypertriglyceridemia 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypoalbuminemia 4/13 (30.8%) 8 0/1 (0%) 0 3/9 (33.3%) 9 1/1 (100%) 3 0/1 (0%) 0 12/22 (54.5%) 27 1/2 (50%) 3 0/1 (0%) 0 1/2 (50%) 5 4/15 (26.7%) 6 2/7 (28.6%) 9 1/1 (100%) 1 2/2 (100%) 6 1/131 (0.8%) 3
    Hypocalcemia 1/13 (7.7%) 2 0/1 (0%) 0 2/9 (22.2%) 2 1/1 (100%) 1 0/1 (0%) 0 3/22 (13.6%) 5 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 4 4/15 (26.7%) 8 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypokalemia 1/13 (7.7%) 1 0/1 (0%) 0 2/9 (22.2%) 5 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 6 0/2 (0%) 0 1/1 (100%) 1 1/2 (50%) 9 3/15 (20%) 3 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypomagnesemia 3/13 (23.1%) 5 0/1 (0%) 0 1/9 (11.1%) 2 1/1 (100%) 5 0/1 (0%) 0 7/22 (31.8%) 10 1/2 (50%) 1 0/1 (0%) 0 1/2 (50%) 2 5/15 (33.3%) 6 3/7 (42.9%) 7 0/1 (0%) 0 1/2 (50%) 4 0/131 (0%) 0
    Hyponatremia 3/13 (23.1%) 9 0/1 (0%) 0 2/9 (22.2%) 3 1/1 (100%) 4 0/1 (0%) 0 5/22 (22.7%) 10 1/2 (50%) 2 0/1 (0%) 0 1/2 (50%) 4 4/15 (26.7%) 6 3/7 (42.9%) 11 0/1 (0%) 0 2/2 (100%) 11 1/131 (0.8%) 1
    Hypophosphatemia 2/13 (15.4%) 2 0/1 (0%) 0 3/9 (33.3%) 6 1/1 (100%) 1 0/1 (0%) 0 3/22 (13.6%) 6 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 5 5/15 (33.3%) 7 2/7 (28.6%) 2 1/1 (100%) 1 0/2 (0%) 0 1/131 (0.8%) 2
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Arthritis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Back pain 1/13 (7.7%) 2 1/1 (100%) 2 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 3 1/2 (50%) 1 0/15 (0%) 0 3/7 (42.9%) 5 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Bone pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Chest wall pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Flank pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Generalized muscle weakness 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Muscle weakness lower limb 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Muscle weakness right-sided 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Muscle weakness upper limb 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, Bilateral Arm Pain 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, Other, cramping in legs 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, muscle cramping 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, muscle weakness 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, right shoulder pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Musculoskeletal and connective tissue disorder - Other, tendonitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Myalgia 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 2 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Specify 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Tumor pain 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 2 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 2 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Nervous system disorders
    Depressed level of consciousness 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Dizziness 2/13 (15.4%) 3 1/1 (100%) 4 1/9 (11.1%) 1 1/1 (100%) 2 0/1 (0%) 0 3/22 (13.6%) 4 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 2/7 (28.6%) 2 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Dysarthria 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Dysgeusia 3/13 (23.1%) 3 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 2/7 (28.6%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Headache 3/13 (23.1%) 3 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 4 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 3/15 (20%) 3 4/7 (57.1%) 4 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Intracranial hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Nervous system disorders - Other, vocal cord paralysis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Nervous system disorders - Other, Vasomotor Instability 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Paresthesia 0/13 (0%) 0 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Peripheral motor neuropathy 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Peripheral sensory neuropathy 0/13 (0%) 0 1/1 (100%) 1 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Spasticity 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Psychiatric disorders
    Anxiety 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Delirium 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Depression 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 2 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Insomnia 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 3/7 (42.9%) 4 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Psychiatric disorders - Other, labile mood; TMZ 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Renal and urinary disorders
    Hematuria 1/13 (7.7%) 2 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/22 (9.1%) 2 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 2 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hemoglobinuria 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Proteinuria 1/13 (7.7%) 1 0/1 (0%) 0 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 3 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Renal and urinary disorders - Other, Dysuria 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Renal and urinary disorders - Other, rectal pressure 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Urinary frequency 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Urinary urgency 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Reproductive system and breast disorders
    Pelvic pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vaginal discharge 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vaginal hemorrhage 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vaginal pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 5 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 3/15 (20%) 3 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/131 (0.8%) 1
    Dyspnea 2/13 (15.4%) 2 1/1 (100%) 2 2/9 (22.2%) 2 0/1 (0%) 0 0/1 (0%) 0 5/22 (22.7%) 9 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 1/15 (6.7%) 1 2/7 (28.6%) 2 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Epistaxis 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 2 0/131 (0%) 0
    Hiccups 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hoarseness 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Nasal congestion 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 2 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Pleural effusion 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 1/2 (50%) 2 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Pleuritic pain 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Pneumonitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 1/22 (4.5%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Postnasal drip 0/13 (0%) 0 1/1 (100%) 1 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Productive cough 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, Bleeding in Plueral Fluid 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Respiratory, thoracic and mediastinal disorders - Other, viral illness 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Sore throat 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/131 (0%) 0
    Wheezing 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders
    Dry skin 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/22 (13.6%) 3 1/2 (50%) 1 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hyperhidrosis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Palmar-plantar erythrodysesthesia syndrome 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Papulopustular rash 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Pruritus 0/13 (0%) 0 1/1 (100%) 1 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 4/22 (18.2%) 4 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 1/7 (14.3%) 1 0/1 (0%) 0 1/2 (50%) 1 0/131 (0%) 0
    Rash acneiform 0/13 (0%) 0 0/1 (0%) 0 2/9 (22.2%) 3 0/1 (0%) 0 1/1 (100%) 1 8/22 (36.4%) 12 2/2 (100%) 2 1/1 (100%) 1 1/2 (50%) 1 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 2/2 (100%) 4 0/131 (0%) 0
    Rash maculo-papular 0/13 (0%) 0 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 1/1 (100%) 1 10/22 (45.5%) 11 0/2 (0%) 0 1/1 (100%) 1 1/2 (50%) 1 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, ingrown toe nail 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, lip sore & paronychia cuticles 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 1/2 (50%) 1 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, ecchymosis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, erythema 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, hemorrhage 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, pruritic rash 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 1/7 (14.3%) 1 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, rash-protuberant 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, redness of left hand 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, redness, left hand 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, redness,left hand 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, skin cracking 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin and subcutaneous tissue disorders - Other, skin pallor 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Skin ulceration 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Vascular disorders
    Hot flashes 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 1/1 (100%) 1 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Hypertension 8/13 (61.5%) 8 0/1 (0%) 0 1/9 (11.1%) 3 0/1 (0%) 0 0/1 (0%) 0 5/22 (22.7%) 13 2/2 (100%) 10 1/1 (100%) 1 1/2 (50%) 1 1/15 (6.7%) 2 2/7 (28.6%) 9 0/1 (0%) 0 1/2 (50%) 2 0/131 (0%) 0
    Hypotension 1/13 (7.7%) 1 0/1 (0%) 0 1/9 (11.1%) 1 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 3 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 1/15 (6.7%) 1 2/7 (28.6%) 3 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Superficial thrombophlebitis 0/13 (0%) 0 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/22 (4.5%) 1 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0
    Thromboembolic event 1/13 (7.7%) 1 0/1 (0%) 0 0/9 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/22 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/15 (0%) 0 0/7 (0%) 0 0/1 (0%) 0 0/2 (0%) 0 0/131 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Dr. Alice P. Chen
    Organization National Cancer Institute
    Phone 240-781-3274
    Email chenali@mail.nih.gov
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01827384
    Other Study ID Numbers:
    • NCI-2013-01588
    • NCI-2013-01588
    • MPACT
    • 130105
    • P121047
    • 9149
    • 9149
    • ZIABC011078
    First Posted:
    Apr 9, 2013
    Last Update Posted:
    May 10, 2022
    Last Verified:
    Apr 1, 2022