Alisertib (MLN8237) in Participants With Ovarian, Fallopian Tube or Peritoneal Cancer Preceded by Phase 1 Study of MLN8237 Plus Paclitaxel Treatment of Ovary or Breast Cancer

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01091428
Collaborator
(none)
191
4
4
87.1
47.8
0.5

Study Details

Study Description

Brief Summary

This is an open-label, multicenter study with a nonrandomized Phase 1 portion and an open-label, randomized, Phase 2 portion evaluating MLN8237 in combination with weekly paclitaxel in adult female participants with advanced breast cancer (Phase 1 portion only) and recurrent ovarian cancer (both Phase 1 and Phase 2 portions).

Detailed Description

The drug tested in this study was called alisertib. Alisertib was tested to treat people who have ovarian and breast cancer. This study looked at safety, any anti-tumor effect, and it also determined a recommended dose of alisertib plus paclitaxel to take into further studies. Pharmacokinetic blood samples were studied to characterize any effects on the concentration of each of the drugs when administered together.

The study enrolled 191 patients. Participants with Breast Cancer and Ovarian Cancer received one of the following escalating doses of alisertib in combination with paclitaxel in the

Phase 1 lead-in portion of the study:
  • Alisertib 10 mg BID + Paclitaxel 80 mg/m^2

  • Alisertib 20 mg BID + Paclitaxel 80 mg/m^2

  • Alisertib 20 mg BID + Paclitaxel 60 mg/m^2

  • Alisertib 30 mg BID + Paclitaxel 60 mg/m^2

  • Alisertib 40 mg BID + Paclitaxel 60 mg/m^2

  • Alisertib 50 mg BID + Paclitaxel 60 mg/m^2

Once the maximum tolerated dose (MTD)/ recommended phase 2 dose (RP2D) was determined, participants were randomized to receive the following treatments in the Phase 2 portion of the study:

  • Alisertib 40 mg BID + Paclitaxel 60 mg/m^2

  • Paclitaxel 80 mg/m^2

This multi-center trial was conducted in the United States, Poland and France. The overall time to participate in this study was approximately 5 years. Participants made multiple visits to the clinic, and who did not experience disease progression (PD) were followed off-treatment once every 8 weeks until the occurrence of 110 progression-free survival (PFS) events.

Study Design

Study Type:
Interventional
Actual Enrollment :
191 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Randomized Phase 2 Study of MLN8237, an Aurora A Kinase Inhibitor, Plus Weekly Paclitaxel or Weekly Paclitaxel Alone in Patients With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer, Preceded by a Phase 1 Portion in Patients With Ovarian or Breast Cancer
Actual Study Start Date :
Apr 16, 2010
Actual Primary Completion Date :
Aug 12, 2014
Actual Study Completion Date :
Jul 19, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alisertib (Phase 1 - Ovarian cancer)

Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).

Drug: Alisertib
Alisertib tablets
Other Names:
  • MLN8237
  • Drug: Paclitaxel
    Paclitaxel intravenous infusion

    Experimental: Alisertib (Phase 1 - Breast cancer)

    Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).

    Drug: Alisertib
    Alisertib tablets
    Other Names:
  • MLN8237
  • Drug: Paclitaxel
    Paclitaxel intravenous infusion

    Experimental: Alisertib 40 mg BID+Paclitaxel 60 mg/m^2 (Phase 2)

    Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).

    Drug: Alisertib
    Alisertib tablets
    Other Names:
  • MLN8237
  • Drug: Paclitaxel
    Paclitaxel intravenous infusion

    Experimental: Paclitaxel 80 mg/m^2 (Phase 2)

    Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).

    Drug: Paclitaxel
    Paclitaxel intravenous infusion

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) for Alisertib in Combination With Paclitaxel [Cycle 1 (Up to 28 days)]

      The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT). DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.02 and was defined as any of the following events: 1. Grade 4 neutropenia and thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 2 with appropriate treatment; 6. Other alisertib-related nonhematologic toxicities ≥Grade 2 that, in opinion of investigator, required a dose reduction or discontinuation of therapy with alisertib.

    2. Phase 1: MTD and RP2D for Paclitaxel in Combination With Alisertib [Cycle 1 (Up to 28 days)]

      The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of cycle 1).

    3. Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [First dose to 30 days past last dose (Up to 36 Months)]

      An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

    4. Phase 1: Number of Participants With Clinically Significant Laboratory Values [First dose to 30 days past last dose (Up to 36 Months)]

      Abnormal clinical laboratory values (serum chemistry, hematology and urinalysis) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.

    5. Phase 1: Number of Participants With Clinically Significant Vital Sign Findings [First dose to 30 days past last dose (Up to 36 Months)]

      Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.

    6. Phase 1: Number of Participants With Hypersensitivity and Neurotoxicity [Baseline up to Month 36]

    7. Phase 2: Progression-Free Survival (PFS) [At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)]

      PFS is defined as the time from the date randomization for Phase 2 participants to the date of first documented progressive disease (PD) or death as assessed by the investigator using both RECIST 1.1 criteria and CA-125 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125.

    Secondary Outcome Measures

    1. Phase 1: Combined Best Overall Response Rate (ORR) in Participants With Recurrent Ovarian Cancer or Breast Cancer [At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)]

      Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of > 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).

    2. Cmax: Maximum Observed Concentration for Alisertib in Phase 1 [Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose]

    3. Tmax: Time to First Occurrence of Cmax for Alisertib in Phase 1 [Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose]

    4. AUC(Tau): Area Under the Concentration-Time Curve During a Dosing Interval for Alisertib in Phase 1 [Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose]

    5. AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Phase 1 [Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose]

    6. Cmax: Maximum Observed Concentration for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    7. AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    8. AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    9. t½: Terminal Half-Life for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    10. CL: Total Clearance After Intravenous Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    11. Vss: Volume of Distribution at Steady State for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    12. Vz: Volume of Distribution During the Terminal Disposition Phase for Paclitaxel in Phase 1 [Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion]

    13. Phase 2: Combined Best Overall Response Rate (ORR) [At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)]

      Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of > 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).

    14. Phase 2: Duration of Response (DOR) [Up to data-cut off: 12 August 2014 (approximately 24 months)]

      DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD or the last response assessment that is stable disease (SD) or better for a participant who started alternate therapy without progression. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or per CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. A responder that did not experience disease progression is censored at the last response assessment that is SD.

    15. Phase 2: Time to Disease Progression (TTP) [Up to data-cut off: 12 August 2014 (approximately 24 months)]

      TTP was defined as the time from the date of randomization to the date of first documentation of PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or per CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125.

    16. Phase 2: Overall Survival (OS) [Up to data-cut off: 12 August 2014 (approximately 24 months)]

      OS was defined as the time form the date of the randomization to the date of death.

    17. Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [First dose to 30 days past last dose (Up to 27 Months)]

      An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

    18. Phase 2: Number of Participants With Clinically Significant Laboratory Values [First dose to 30 days past last dose (Up to 27 Months)]

      Abnormal clinical laboratory values (serum chemistry, hematology and urinalysis) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.

    19. Phase 2: Number of Participants With Clinically Significant Vital Sign Findings [First dose to 30 days past last dose (Up to 27 Months)]

      Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.

    Other Outcome Measures

    1. Banked Tumor Specimens for Candidate Markers of Response to Alisertib and Taxanes [Up to 24 Months]

    Eligibility Criteria

    Criteria

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

    Each participant must meet all of the following inclusion criteria to be enrolled in the study:

    • Female participants 18 years or older

    • Previously treated, metastatic or locally recurrent malignancy with 1 of the following diagnoses, which has been confirmed histologically or cytologically: adenocarcinoma of the breast (Phase 1 only), recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (Phase 1 and 2)

    • In the Phase 1 portion of the study, participants with breast cancer must have received treatment with at least 1 but no more than 4 prior chemotherapy regimens not including regimens received in the neoadjuvant and/or adjuvant setting

    • Participants with breast cancer must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    • No antineoplastic therapy or radiotherapy within 3 weeks before enrollment (2 weeks for regimens with recovery expected within 7 to 14 days) and recovered from toxicities of prior therapy (except alopecia); the participant must have recovered from all treatment-related toxicities and must have evidence of progressive disease (PD) or persistent disease

    • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

    • Adequate bone marrow, liver and renal function

    • Postmenopausal at least 1 year, OR Surgically sterile, OR If childbearing potential, agree to 2 effective methods of nonhormonal contraception, or agree to completely abstain from heterosexual intercourse

    • Able to provide written informed consent

    • Willing to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures

    • Suitable venous access

    Specific Inclusion Criteria for participants with Recurrent Ovarian, Fallopian Tube or

    Peritoneal Cancer:
    • Prior treatments must have included a platinum and a taxane; the most recent treatment need not be a platinum-containing or taxane-containing regimen

    • Disease must have recurred ≤ 12 months after discontinuation of platinum therapy

    • Participants who previously received weekly taxane are potentially eligible, provided that they did not progress during therapy or within 3 months of completing therapy

    • Participants with platinum-refractory disease, as defined by progression during primary or subsequent platinum-based therapy or persistent radiographic disease after primary or subsequent platinum-based therapy, will be included

    • Participants must have measurable disease in target lesions or assessable disease (defined by cancer antigen-125 - CA-125 per protocol), and disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or modified Gynecologic Cancer Intergroup (GCIG) CA-125 criteria

    Exclusion Criteria:

    Participants meeting any of the following exclusion criteria are not to be enrolled in the study:

    • Prior treatment with an Aurora A-targeted agent (including MLN8237)

    • Treatment with clinically significant enzyme inducers within 14 days prior to the first dose of MLN8237 and during the study

    • Treatment with more than 4 cytotoxic chemotherapy regimens in the metastatic setting; prior therapy cannot include more than 2 prior taxane-containing regimen. Current use of tamoxifen, thalidomide, or any agent used as maintenance or consolidation therapy for OC.

    • Known hypersensitivity to Cremophor® EL, paclitaxel or its components

    • Prior history of ≥ Grade 2 neurotoxicity or any toxicity requiring discontinuation from taxane chemotherapy that is not resolved to ≤ Grade 1

    • Comorbid or unresolved toxicity that would preclude administration of weekly paclitaxel

    • Primary central nervous system malignancy or carcinomatous meningitis

    • Symptomatic brain metastasis

    • Inability to swallow oral medications or maintain a fast

    • History of hemorrhagic or thrombotic cerebrovascular event in past 12 months

    • Surgery within 3 weeks before study enrollment and not fully recovered

    • Diagnosis or treatment of another malignancy within 2 years preceding first dose of MLN8237 and have any evidence of residual disease except nonmelanoma skin cancer or in situ malignancy completely resected

    • Pregnant or lactating

    • Serious illness that could interfere with protocol completion

    • Investigational treatment 21 days prior to first dose of MLN8237

    • Prior allogeneic bone marrow or organ transplantation

    • Infection requiring systemic antibiotic therapy within 14 days prior to first dose of MLN8237

    • Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C

    • Radiotherapy to > 25% bone marrow or whole pelvic radiotherapy

    • Requirement for constant administration of proton pump inhibitor, H2 antagonist, or pancreatic enzymes. Intermittent uses of antacids of H2 antagonists are allowed

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Bronx New York United States
    2 Philadelphia Pennsylvania United States
    3 Houston Texas United States
    4 Seattle Washington United States

    Sponsors and Collaborators

    • Millennium Pharmaceuticals, Inc.

    Investigators

    • Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Millennium Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01091428
    Other Study ID Numbers:
    • C14008
    • 2009-011428-79
    • U1111-1191-6584
    First Posted:
    Mar 24, 2010
    Last Update Posted:
    Jun 4, 2018
    Last Verified:
    May 1, 2018
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Millennium Pharmaceuticals, Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 33 investigative sites in France, Poland and the United States from 16 April 2010 to 19 July 2017. Data cutoff for the primary analysis was 12 August 2014.
    Pre-assignment Detail Participants with a diagnosis of ovarian cancer or breast cancer were enrolled equally in a dose escalation study to determine the recommended Phase 2 dose. In Phase 2 participants were randomized equally to receive alisertib 40 mg BID + paclitaxel 60 mg/m^2 or single agent paclitaxel 80 mg/m^2.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
    Period Title: Phase 1
    STARTED 38 11 0 0
    COMPLETED 0 0 0 0
    NOT COMPLETED 38 11 0 0
    Period Title: Phase 1
    STARTED 0 0 73 69
    COMPLETED 0 0 0 0
    NOT COMPLETED 0 0 73 69

    Baseline Characteristics

    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2) Total
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Total of all reporting groups
    Overall Participants 38 11 73 69 191
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    55.8
    (10.29)
    58.6
    (10.06)
    61.0
    (11.60)
    60.8
    (8.41)
    59.8
    (10.32)
    Sex: Female, Male (Count of Participants)
    Female
    38
    100%
    11
    100%
    73
    100%
    69
    100%
    191
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    Hispanic or Latino
    4
    10.5%
    0
    0%
    1
    1.4%
    4
    5.8%
    9
    4.7%
    Not Hispanic or Latino
    34
    89.5%
    10
    90.9%
    64
    87.7%
    62
    89.9%
    170
    89%
    Not Reported
    0
    0%
    1
    9.1%
    7
    9.6%
    3
    4.3%
    11
    5.8%
    Missing
    0
    0%
    0
    0%
    1
    1.4%
    0
    0%
    1
    0.5%
    Race/Ethnicity, Customized (participants) [Number]
    White
    34
    89.5%
    11
    100%
    66
    90.4%
    55
    79.7%
    166
    86.9%
    Black or African American
    3
    7.9%
    0
    0%
    2
    2.7%
    6
    8.7%
    11
    5.8%
    Asian
    1
    2.6%
    0
    0%
    1
    1.4%
    2
    2.9%
    4
    2.1%
    American Indian or Alaskan Native
    0
    0%
    0
    0%
    0
    0%
    2
    2.9%
    2
    1%
    Other
    0
    0%
    0
    0%
    1
    1.4%
    1
    1.4%
    2
    1%
    Not Reported
    0
    0%
    0
    0%
    2
    2.7%
    3
    4.3%
    5
    2.6%
    Missing
    0
    0%
    0
    0%
    1
    1.4%
    0
    0%
    1
    0.5%
    Region of Enrollment (participants) [Number]
    United States
    38
    100%
    11
    100%
    48
    65.8%
    45
    65.2%
    142
    74.3%
    Poland
    0
    0%
    0
    0%
    10
    13.7%
    8
    11.6%
    18
    9.4%
    France
    0
    0%
    0
    0%
    15
    20.5%
    16
    23.2%
    31
    16.2%
    Height (cm) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm]
    164.2
    (6.41)
    164.5
    (6.38)
    162.4
    (7.02)
    161.9
    (7.30)
    162.7
    (6.99)
    Weight (kg) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg]
    75.86
    (16.41)
    76.29
    (7.29)
    70.42
    (14.78)
    72.50
    (18.71)
    72.59
    (16.37)
    Body Surface Area (m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [m^2]
    1.850
    (0.21)
    1.865
    (0.10)
    1.776
    (0.20)
    1.794
    (0.24)
    1.802
    (0.21)

    Outcome Measures

    1. Primary Outcome
    Title Phase 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) for Alisertib in Combination With Paclitaxel
    Description The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT). DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.02 and was defined as any of the following events: 1. Grade 4 neutropenia and thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 2 with appropriate treatment; 6. Other alisertib-related nonhematologic toxicities ≥Grade 2 that, in opinion of investigator, required a dose reduction or discontinuation of therapy with alisertib.
    Time Frame Cycle 1 (Up to 28 days)

    Outcome Measure Data

    Analysis Population Description
    DLT-Evaluable Population was defined as all participants in the phase 1 who either experienced DLT during Cycle 1 or completed treatment with at least 15 of the planned 18 doses of alisertib and 2 of the planned 3 doses of paclitaxel in Cycle 1 and had sufficient follow-up data.
    Arm/Group Title Alisertib + Paclitaxel (Phase 1)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 49
    Number [mg]
    40
    2. Primary Outcome
    Title Phase 1: MTD and RP2D for Paclitaxel in Combination With Alisertib
    Description The RP2D is the maximum tolerated dose (MTD) or less. The MTD is defined as the dose range at which ≤ 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of cycle 1).
    Time Frame Cycle 1 (Up to 28 days)

    Outcome Measure Data

    Analysis Population Description
    DLT-Evaluable Population was defined as all participants in the phase 1 who either experienced DLT during Cycle 1 or completed treatment with at least 15 of the planned 18 doses of alisertib and 2 of the planned 3 doses of paclitaxel in Cycle 1 and had sufficient follow-up data.
    Arm/Group Title Alisertib + Paclitaxel
    Arm/Group Description Paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.
    Measure Participants 49
    Number [mg/m^2]
    60
    3. Primary Outcome
    Title Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
    Time Frame First dose to 30 days past last dose (Up to 36 Months)

    Outcome Measure Data

    Analysis Population Description
    Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 38 11
    AEs
    38
    100%
    11
    100%
    SAEs
    13
    34.2%
    2
    18.2%
    4. Primary Outcome
    Title Phase 1: Number of Participants With Clinically Significant Laboratory Values
    Description Abnormal clinical laboratory values (serum chemistry, hematology and urinalysis) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
    Time Frame First dose to 30 days past last dose (Up to 36 Months)

    Outcome Measure Data

    Analysis Population Description
    Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 38 11
    Neutrophil count decreased
    3
    7.9%
    0
    0%
    White blood cell count decreased
    1
    2.6%
    1
    9.1%
    Aspartate aminotransferase increased
    3
    7.9%
    1
    9.1%
    Alanine aminotransferase increased
    2
    5.3%
    0
    0%
    Ammonia increased
    1
    2.6%
    0
    0%
    Transaminases increased
    1
    2.6%
    0
    0%
    Blood alkaline phosphatase increased
    1
    2.6%
    1
    9.1%
    High density lipoprotein decreased
    1
    2.6%
    0
    0%
    Urine output decreased
    1
    2.6%
    0
    0%
    Granulocyte count decreased
    0
    0%
    1
    9.1%
    5. Primary Outcome
    Title Phase 1: Number of Participants With Clinically Significant Vital Sign Findings
    Description Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
    Time Frame First dose to 30 days past last dose (Up to 36 Months)

    Outcome Measure Data

    Analysis Population Description
    Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 38 11
    Pyrexia
    8
    21.1%
    5
    45.5%
    Heart rate irregular
    1
    2.6%
    0
    0%
    Blood pressure increased
    0
    0%
    1
    9.1%
    Weight decreased
    3
    7.9%
    0
    0%
    6. Primary Outcome
    Title Phase 1: Number of Participants With Hypersensitivity and Neurotoxicity
    Description
    Time Frame Baseline up to Month 36

    Outcome Measure Data

    Analysis Population Description
    Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 38 11
    Hypersensitivity
    1
    2.6%
    0
    0%
    Neurotoxicity
    0
    0%
    0
    0%
    7. Primary Outcome
    Title Phase 2: Progression-Free Survival (PFS)
    Description PFS is defined as the time from the date randomization for Phase 2 participants to the date of first documented progressive disease (PD) or death as assessed by the investigator using both RECIST 1.1 criteria and CA-125 criteria. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125.
    Time Frame At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)

    Outcome Measure Data

    Analysis Population Description
    The modified intent-to-treat (mITT) population was defined as all participants who were randomized and received at least 1 dose of any study drug. For a participant that has not progressed and has not died or has started the alternate therapy, PFS is censored at the last response assessment that is stable disease (SD) or better.
    Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 73 69
    Median (80% Confidence Interval) [days]
    204
    142
    8. Secondary Outcome
    Title Phase 1: Combined Best Overall Response Rate (ORR) in Participants With Recurrent Ovarian Cancer or Breast Cancer
    Description Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of > 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).
    Time Frame At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)

    Outcome Measure Data

    Analysis Population Description
    Response evaluable population was defined as all participants who were randomized and had measurable disease according to RECIST or assessable disease by CA-125 criteria, who received at least 1 dose of any study drug, and who had at least 1 available post-Baseline response assessment as per either RECIST or CA-125 criteria.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles). Participants with breast cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 38 11
    Number (80% Confidence Interval) [percentage of participants]
    47
    123.7%
    55
    500%
    9. Secondary Outcome
    Title Cmax: Maximum Observed Concentration for Alisertib in Phase 1
    Description
    Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle1 (Day1)
    428.7
    (189.59)
    766.8
    (312.10)
    900.00
    (392.17)
    1365.3
    (466.51)
    1398.7
    (607.70)
    1960.0
    (515.65)
    Cycle1 (Day3)
    594.3
    (228.46)
    1042.3
    (280.95)
    871.3
    (268.23)
    1708.5
    (820.54)
    2493.4
    (955.31)
    4456.7
    (947.33)
    10. Secondary Outcome
    Title Tmax: Time to First Occurrence of Cmax for Alisertib in Phase 1
    Description
    Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    3.0
    (189.59)
    3.1
    (312.10)
    2.6
    (392.17)
    2.5
    (466.51)
    3.0
    (607.70)
    2.0
    (515.65)
    Cycle 1, Day 3
    2.2
    (228.46)
    3.0
    (280.95)
    3.5
    (268.23)
    2.0
    (820.54)
    2.0
    (955.31)
    2.0
    (947.33)
    11. Secondary Outcome
    Title AUC(Tau): Area Under the Concentration-Time Curve During a Dosing Interval for Alisertib in Phase 1
    Description
    Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    2519.3
    (937.52)
    5175.0
    (1766.11)
    5610.0
    (2105.42)
    8581.7
    (3225.64)
    9594.0
    (4600.42)
    14666.7
    (3707.20)
    Cycle 1, Day3
    3966.7
    (1112.11)
    7745.0
    (2233.91)
    6155.0
    (1737.69)
    12478.3
    (6013.93)
    17557.3
    (7856.30)
    35500.0
    (12842.12)
    12. Secondary Outcome
    Title AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Phase 1
    Description
    Time Frame Days 1 and 3 in Cycle 1: pre-dose and at multiple timepoints (up to 12 hours) post morning dose

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for alisertib was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and alisertib concentration-time data to permit noncompartmental PK analysis.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    2519.3
    (937.52)
    5175.0
    (1766.11)
    5610.0
    (2105.42)
    8581.7
    (3225.64)
    9594.0
    (4600.42)
    14666.7
    (3707.20)
    Cycle 1, Day 3
    3966.7
    (1112.11)
    7745.0
    (2233.91)
    6155.0
    (1737.69)
    12478.3
    (6013.93)
    17557.3
    (7856.30)
    35500.0
    (12842.12)
    13. Secondary Outcome
    Title Cmax: Maximum Observed Concentration for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    3097.3
    (1114.51)
    3120.0
    (447.75)
    2117.5
    (745.54)
    2448.0
    (988.65)
    1917.3
    (528.32)
    1338.7
    (617.94)
    Cycle 2, Day 1
    2654.6
    (696.45)
    3231.7
    (615.64)
    1733.3
    (541.97)
    2478.3
    (878.39)
    1492.7
    (558.14)
    1750.0
    (183.85)
    14. Secondary Outcome
    Title AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    4437.7
    (1053.87)
    4825.0
    (735.17)
    3355.0
    (865.89)
    3366.0
    (1139.25)
    2652.7
    (651.32)
    2190.0
    (387.43)
    Cycle 2, Day 1
    4061.7
    (1298.86)
    5301.7
    (1183.31)
    2660.0
    (307.90)
    3056.0
    (812.67)
    2231.5
    (604.76)
    2460.0
    (14.14)
    15. Secondary Outcome
    Title AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    5317.8
    (1052.40)
    5238.0
    (812.26)
    3860.0
    (824.20)
    3375.0
    (1130.56)
    3175.5
    (933.10)
    2535.0
    (657.61)
    Cycle 2, Day 1
    4606.4
    (1391.35)
    5584.0
    (1367.51)
    3185.0
    (176.78)
    3415.0
    (1010.82)
    2680.0
    (607.22)
    16. Secondary Outcome
    Title t½: Terminal Half-Life for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    17.2
    (4.20)
    17.5
    (1.87)
    17.3
    (4.16)
    13.9
    (4.68)
    16.8
    (6.83)
    18.4
    (8.70)
    Cycle 2, Day 1
    17.0
    (3.63)
    16.2
    (5.05)
    17.3
    (5.23)
    16.5
    (4.32)
    13.3
    (5.59)
    14.6
    (2.19)
    17. Secondary Outcome
    Title CL: Total Clearance After Intravenous Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    29.756
    (6.8175)
    28.220
    (5.1804)
    26.800
    (7.5386)
    40.950
    (17.5268)
    38.055
    (13.7095)
    38.950
    (11.2430)
    Cycle 2, Day 1
    35.827
    (10.4005)
    28.240
    (7.3748)
    33.900
    (5.2326)
    34.250
    (8.2614)
    42.440
    (10.4296)
    18. Secondary Outcome
    Title Vss: Volume of Distribution at Steady State for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    313.444
    (118.6593)
    310.800
    (86.9235)
    330.000
    (208.8851)
    357.000
    (158.1834)
    433.909
    (179.7757)
    460.500
    (103.9447)
    Cycle 2, Day 1
    391.364
    (64.3137)
    283.200
    (121.1123)
    413.500
    (242.5376)
    377.000
    (118.9650)
    372.600
    (180.7332)
    19. Secondary Outcome
    Title Vz: Volume of Distribution During the Terminal Disposition Phase for Paclitaxel in Phase 1
    Description
    Time Frame Day 1 in Cycles 1 and 2: pre-infusion and at multiple timepoints (up to 47 hours) post-infusion

    Outcome Measure Data

    Analysis Population Description
    PK analysis set for paclitaxel was defined as all participants in the phase 1 portion of the study for whom there was sufficient dosing and paclitaxel concentration time data to permit noncompartmental PK analysis. Number analyzed is the number of participants with evaluable data at the specified time-point.
    Arm/Group Title Alisertib 10 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 80 mg/m^2 Alisertib 20 mg BID + Paclitaxel 60 mg/m^2 Alisertib 30 mg BID + Paclitaxel 60 mg/m^2 Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 Alisertib 50 mg BID + Paclitaxel 60 mg/m^2
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 30 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1
    Measure Participants 15 6 4 6 15 3
    Cycle 1, Day 1
    705.000
    (179.0223)
    721.600
    (203.8021)
    694.000
    (352.1534)
    850.500
    (291.0401)
    872.727
    (328.6202)
    956.500
    (188.7975)
    Cycle 2, Day 1
    829.364
    (156.6060)
    663.200
    (321.3070)
    865.500
    (388.2016)
    777.250
    (103.7027)
    733.000
    (208.4898)
    20. Secondary Outcome
    Title Phase 2: Combined Best Overall Response Rate (ORR)
    Description Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must have been confirmed by a fourth sample 28 days later (a total of 4 samples required) or A serial decrease of > 75% over 3 samples; the third sample was to be obtained 28 days after the second (a total of 3 samples required).
    Time Frame At the end of Cycle 2 and at the completion of every 2 cycles until PD was documented or up to data cut-off: 12 August 2014 (approximately 24 months)

    Outcome Measure Data

    Analysis Population Description
    Response evaluable population was defined as all participants who were randomized and had measurable disease according to RECIST or assessable disease by CA-125 criteria, who received at least 1 dose of any study drug, and who had at least 1 available post-Baseline response assessment as per either RECIST or CA-125 criteria.
    Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 67 64
    Number (80% Confidence Interval) [percentage of participants]
    60
    157.9%
    52
    472.7%
    21. Secondary Outcome
    Title Phase 2: Duration of Response (DOR)
    Description DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD or the last response assessment that is stable disease (SD) or better for a participant who started alternate therapy without progression. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or per CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. A responder that did not experience disease progression is censored at the last response assessment that is SD.
    Time Frame Up to data-cut off: 12 August 2014 (approximately 24 months)

    Outcome Measure Data

    Analysis Population Description
    Participants from Response evaluable population, all participants who were randomized and had measurable disease according to RECIST 1.1 or assessable disease by CA-125 criteria, who received at least 1 dose of any study drug, and who had at least 1 available post-Baseline response assessment per RECIST 1.1 or CA-125 criteria, who were responders.
    Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 40 33
    Median (80% Confidence Interval) [days]
    201
    169
    22. Secondary Outcome
    Title Phase 2: Time to Disease Progression (TTP)
    Description TTP was defined as the time from the date of randomization to the date of first documentation of PD. PD is defined as 20% increase in the sum of the longest diameter of target lesions for measurable neoplastic disease or per CA-125 criteria with elevated (>70 units/mL) levels on 2 occasions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level > 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125.
    Time Frame Up to data-cut off: 12 August 2014 (approximately 24 months)

    Outcome Measure Data

    Analysis Population Description
    mITT Population was defined as all participants who were randomized and received at least 1 dose of any study drug. For a participant that has not progressed, TTP is censored at the last response assessment that is SD or better
    Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 73 69
    Median (80% Confidence Interval) [days]
    204
    142
    23. Secondary Outcome
    Title Phase 2: Overall Survival (OS)
    Description OS was defined as the time form the date of the randomization to the date of death.
    Time Frame Up to data-cut off: 12 August 2014 (approximately 24 months)

    Outcome Measure Data

    Analysis Population Description
    mITT Population was defined as all participants who were randomized and received at least 1 dose of any study drug. For a participant that is alive, OS will be censored at the last known date.
    Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 73 69
    Median (80% Confidence Interval) [days]
    NA
    NA
    24. Secondary Outcome
    Title Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    Description An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
    Time Frame First dose to 30 days past last dose (Up to 27 Months)

    Outcome Measure Data

    Analysis Population Description
    Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 73 69
    AEs
    73
    192.1%
    66
    600%
    SAEs
    30
    78.9%
    19
    172.7%
    25. Secondary Outcome
    Title Phase 2: Number of Participants With Clinically Significant Laboratory Values
    Description Abnormal clinical laboratory values (serum chemistry, hematology and urinalysis) were reported as AEs if they were considered by the investigator to be a clinically significant change from Baseline or led to premature discontinuation of study treatment, dose modification, or other therapeutic intervention.
    Time Frame First dose to 30 days past last dose (Up to 27 Months)

    Outcome Measure Data

    Analysis Population Description
    Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 73 69
    Neutrophil count decreased
    14
    36.8%
    4
    36.4%
    White blood cell count decreased
    6
    15.8%
    1
    9.1%
    Lymphocyte count decreased
    1
    2.6%
    1
    9.1%
    Aspartate aminotransferase increased
    1
    2.6%
    3
    27.3%
    Alanine aminotransferase increased
    1
    2.6%
    4
    36.4%
    Gamma-glutamyltransferase increased
    0
    0%
    1
    9.1%
    Blood alkaline phosphatase increased
    2
    5.3%
    2
    18.2%
    Haemoglobin decreased
    3
    7.9%
    1
    9.1%
    Blood magnesium decreased
    0
    0%
    3
    27.3%
    Blood creatinine increased
    1
    2.6%
    2
    18.2%
    Platelet count decreased
    2
    5.3%
    0
    0%
    International normalised ratio increased
    1
    2.6%
    0
    0%
    Blood albumin decreased
    1
    2.6%
    0
    0%
    Troponin T increased
    0
    0%
    1
    9.1%
    26. Secondary Outcome
    Title Phase 2: Number of Participants With Clinically Significant Vital Sign Findings
    Description Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
    Time Frame First dose to 30 days past last dose (Up to 27 Months)

    Outcome Measure Data

    Analysis Population Description
    Safety population was defined as all participants who received at least 1 dose of any study drug.
    Arm/Group Title Alisertib 40 mg BID + Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2.
    Measure Participants 73 69
    Pyrexia
    15
    39.5%
    8
    72.7%
    Heart rate increased
    1
    2.6%
    0
    0%
    Blood pressure increased
    1
    2.6%
    0
    0%
    Weight decreased
    8
    21.1%
    2
    18.2%
    27. Other Pre-specified Outcome
    Title Banked Tumor Specimens for Candidate Markers of Response to Alisertib and Taxanes
    Description
    Time Frame Up to 24 Months

    Outcome Measure Data

    Analysis Population Description
    This Outcome Measure was originally registered as a Secondary but this Outcome Measure was Exploratory and no data was collected.
    Arm/Group Title Alisertib + Paclitaxel (Phase 1)
    Arm/Group Description Participants with ovarian cancer received alisertib (MLN8237) 10, 20, 30 or 40 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 or 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1 (Up to 37 cycles).
    Measure Participants 0

    Adverse Events

    Time Frame Phase 1: First dose to 30 days past last dose (Up to 36 Months); Phase 2: First dose to 30 days past last dose (Up to 27 Months)
    Adverse Event Reporting Description At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Arm/Group Title Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Arm/Group Description Alisertib (MLN8237) 10 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 20 mg, orally, twice daily (BID) on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1. Alisertib 40 mg, orally, BID on Days 1-3, 8-10 and 15-17, combined with weekly paclitaxel 60 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles). Paclitaxel 80 mg/m^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 2 (Up to 28 cycles).
    All Cause Mortality
    Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 13/38 (34.2%) 2/11 (18.2%) 30/73 (41.1%) 19/69 (27.5%)
    Blood and lymphatic system disorders
    Febrile neutropenia 6/38 (15.8%) 9 0/11 (0%) 0 9/73 (12.3%) 9 0/69 (0%) 0
    Neutropenia 0/38 (0%) 0 0/11 (0%) 0 6/73 (8.2%) 7 0/69 (0%) 0
    Anaemia 1/38 (2.6%) 1 0/11 (0%) 0 2/73 (2.7%) 4 1/69 (1.4%) 1
    Haemorrhagic anaemia 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Ear and labyrinth disorders
    Hearing impaired 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Gastrointestinal disorders
    Nausea 1/38 (2.6%) 1 0/11 (0%) 0 3/73 (4.1%) 3 2/69 (2.9%) 2
    Vomiting 1/38 (2.6%) 1 0/11 (0%) 0 2/73 (2.7%) 4 2/69 (2.9%) 2
    Intestinal obstruction 0/38 (0%) 0 0/11 (0%) 0 4/73 (5.5%) 4 1/69 (1.4%) 2
    Ileus 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Abdominal pain 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Abdominal pain lower 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Diarrhoea 1/38 (2.6%) 1 0/11 (0%) 0 2/73 (2.7%) 2 1/69 (1.4%) 1
    Small intestinal obstruction 0/38 (0%) 0 0/11 (0%) 0 2/73 (2.7%) 3 2/69 (2.9%) 2
    Constipation 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Stomatitis 0/38 (0%) 0 0/11 (0%) 0 2/73 (2.7%) 2 0/69 (0%) 0
    Abdominal hernia obstructive 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Proctalgia 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Gastric perforation 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Intestinal perforation 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Lower gastrointestinal haemorrhage 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Ascites 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Haemorrhagic ascites 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    General disorders
    Pyrexia 0/38 (0%) 0 1/11 (9.1%) 1 3/73 (4.1%) 3 2/69 (2.9%) 2
    Asthenia 1/38 (2.6%) 1 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Fatigue 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 1/69 (1.4%) 1
    Oedema peripheral 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Hepatobiliary disorders
    Hepatic failure 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Infections and infestations
    Device related infection 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Abscess soft tissue 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 2 0/69 (0%) 0
    Infection 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Pneumonia 0/38 (0%) 0 0/11 (0%) 0 3/73 (4.1%) 3 0/69 (0%) 0
    Bronchitis 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Urinary tract infection 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Pyelonephritis 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Cellulitis 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Catheter site cellulitis 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Sepsis 0/38 (0%) 0 1/11 (9.1%) 1 1/73 (1.4%) 1 1/69 (1.4%) 1
    Gastroenteritis 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Clostridium difficile infection 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Injury, poisoning and procedural complications
    Vascular access complication 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Fall 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Pubis fracture 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Investigations
    Neutrophil count decreased 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    White blood cell count decreased 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Troponin T increased 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Metabolism and nutrition disorders
    Dehydration 0/38 (0%) 0 0/11 (0%) 0 4/73 (5.5%) 4 0/69 (0%) 0
    Hyponatraemia 1/38 (2.6%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Musculoskeletal and connective tissue disorders
    Flank pain 1/38 (2.6%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant pleural effusion 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Nervous system disorders
    Cerebrovascular accident 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Syncope 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Psychiatric disorders
    Confusional state 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Renal and urinary disorders
    Acute kidney injury 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Postrenal failure 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Renal failure 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 0/38 (0%) 0 1/11 (9.1%) 1 2/73 (2.7%) 2 1/69 (1.4%) 1
    Tachypnoea 1/38 (2.6%) 1 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Pulmonary alveolar haemorrhage 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Pleural effusion 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Skin and subcutaneous tissue disorders
    Paraneoplastic dermatomyositis 0/38 (0%) 0 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Vascular disorders
    Deep vein thrombosis 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Venous thrombosis limb 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Hypotension 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Embolism 0/38 (0%) 0 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Other (Not Including Serious) Adverse Events
    Alisertib (Phase 1 - Ovarian Cancer) Alisertib (Phase 1 - Breast Cancer) Alisertib 40 mg BID+ Paclitaxel 60 mg/m^2 (Phase 2) Paclitaxel 80 mg/m^2 (Phase 2)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 38/38 (100%) 11/11 (100%) 73/73 (100%) 64/69 (92.8%)
    Blood and lymphatic system disorders
    Neutropenia 24/38 (63.2%) 100 10/11 (90.9%) 58 52/73 (71.2%) 179 10/69 (14.5%) 17
    Anaemia 22/38 (57.9%) 37 7/11 (63.6%) 13 33/73 (45.2%) 61 20/69 (29%) 36
    Leukopenia 20/38 (52.6%) 47 8/11 (72.7%) 32 11/73 (15.1%) 27 3/69 (4.3%) 6
    Thrombocytopenia 0/38 (0%) 0 2/11 (18.2%) 17 4/73 (5.5%) 7 1/69 (1.4%) 2
    Granulocytopenia 3/38 (7.9%) 4 1/11 (9.1%) 4 0/73 (0%) 0 1/69 (1.4%) 1
    Febrile neutropenia 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Cardiac disorders
    Tachycardia 5/38 (13.2%) 5 1/11 (9.1%) 1 1/73 (1.4%) 1 2/69 (2.9%) 2
    Palpitations 3/38 (7.9%) 5 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Ear and labyrinth disorders
    Ear pain 3/38 (7.9%) 4 0/11 (0%) 0 3/73 (4.1%) 3 1/69 (1.4%) 1
    Ear congestion 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 1/69 (1.4%) 1
    Endocrine disorders
    Hypothyroidism 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Eye disorders
    Dry eye 4/38 (10.5%) 5 2/11 (18.2%) 2 1/73 (1.4%) 1 1/69 (1.4%) 1
    Lacrimation increased 2/38 (5.3%) 2 2/11 (18.2%) 2 2/73 (2.7%) 2 1/69 (1.4%) 1
    Visual impairment 3/38 (7.9%) 3 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Cataract 1/38 (2.6%) 1 1/11 (9.1%) 1 2/73 (2.7%) 2 0/69 (0%) 0
    Eye pruritus 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Vision blurred 2/38 (5.3%) 4 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Vitreous floaters 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Conjunctivitis allergic 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Meibomian gland dysfunction 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Gastrointestinal disorders
    Diarrhoea 27/38 (71.1%) 49 8/11 (72.7%) 11 46/73 (63%) 96 15/69 (21.7%) 19
    Nausea 23/38 (60.5%) 33 5/11 (45.5%) 6 32/73 (43.8%) 54 32/69 (46.4%) 46
    Stomatitis 15/38 (39.5%) 32 8/11 (72.7%) 10 46/73 (63%) 91 6/69 (8.7%) 8
    Constipation 15/38 (39.5%) 22 3/11 (27.3%) 4 26/73 (35.6%) 33 17/69 (24.6%) 23
    Abdominal pain 12/38 (31.6%) 19 3/11 (27.3%) 3 21/73 (28.8%) 39 20/69 (29%) 26
    Vomiting 13/38 (34.2%) 42 4/11 (36.4%) 4 20/73 (27.4%) 31 18/69 (26.1%) 25
    Abdominal pain upper 3/38 (7.9%) 5 1/11 (9.1%) 1 11/73 (15.1%) 12 4/69 (5.8%) 6
    Dyspepsia 5/38 (13.2%) 5 1/11 (9.1%) 1 9/73 (12.3%) 12 3/69 (4.3%) 3
    Abdominal distension 2/38 (5.3%) 2 2/11 (18.2%) 2 9/73 (12.3%) 10 4/69 (5.8%) 4
    Ascites 3/38 (7.9%) 3 1/11 (9.1%) 1 8/73 (11%) 11 5/69 (7.2%) 7
    Haemorrhoids 4/38 (10.5%) 4 0/11 (0%) 0 9/73 (12.3%) 10 2/69 (2.9%) 4
    Gastrooesophageal reflux disease 4/38 (10.5%) 4 0/11 (0%) 0 6/73 (8.2%) 7 4/69 (5.8%) 5
    Oral pain 5/38 (13.2%) 6 0/11 (0%) 0 6/73 (8.2%) 6 0/69 (0%) 0
    Dry mouth 3/38 (7.9%) 3 2/11 (18.2%) 2 1/73 (1.4%) 1 3/69 (4.3%) 3
    Abdominal discomfort 5/38 (13.2%) 6 2/11 (18.2%) 2 1/73 (1.4%) 1 0/69 (0%) 0
    Flatulence 6/38 (15.8%) 9 1/11 (9.1%) 3 1/73 (1.4%) 1 0/69 (0%) 0
    Aphthous stomatitis 0/38 (0%) 0 0/11 (0%) 0 5/73 (6.8%) 9 2/69 (2.9%) 2
    Dysphagia 1/38 (2.6%) 1 1/11 (9.1%) 1 4/73 (5.5%) 6 1/69 (1.4%) 2
    Toothache 2/38 (5.3%) 2 0/11 (0%) 0 2/73 (2.7%) 2 2/69 (2.9%) 4
    Rectal haemorrhage 2/38 (5.3%) 2 0/11 (0%) 0 2/73 (2.7%) 2 0/69 (0%) 0
    Abdominal pain lower 2/38 (5.3%) 4 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 1
    Tongue ulceration 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 2 0/69 (0%) 0
    General disorders
    Fatigue 26/38 (68.4%) 29 8/11 (72.7%) 10 43/73 (58.9%) 82 31/69 (44.9%) 37
    Oedema peripheral 15/38 (39.5%) 24 3/11 (27.3%) 3 12/73 (16.4%) 15 18/69 (26.1%) 25
    Pyrexia 8/38 (21.1%) 11 4/11 (36.4%) 7 13/73 (17.8%) 18 7/69 (10.1%) 10
    Asthenia 5/38 (13.2%) 6 2/11 (18.2%) 2 10/73 (13.7%) 20 8/69 (11.6%) 11
    Chills 10/38 (26.3%) 12 0/11 (0%) 0 6/73 (8.2%) 6 0/69 (0%) 0
    Non-cardiac chest pain 2/38 (5.3%) 2 2/11 (18.2%) 2 3/73 (4.1%) 4 0/69 (0%) 0
    Catheter site pain 3/38 (7.9%) 5 0/11 (0%) 0 2/73 (2.7%) 2 1/69 (1.4%) 1
    Peripheral swelling 2/38 (5.3%) 3 0/11 (0%) 0 2/73 (2.7%) 4 1/69 (1.4%) 1
    Pain 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Chest discomfort 2/38 (5.3%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Early satiety 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Localised oedema 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Immune system disorders
    Seasonal allergy 3/38 (7.9%) 3 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Infections and infestations
    Urinary tract infection 11/38 (28.9%) 29 4/11 (36.4%) 8 11/73 (15.1%) 20 4/69 (5.8%) 7
    Upper respiratory tract infection 11/38 (28.9%) 24 4/11 (36.4%) 4 3/73 (4.1%) 4 4/69 (5.8%) 5
    Sinusitis 3/38 (7.9%) 10 3/11 (27.3%) 3 1/73 (1.4%) 1 2/69 (2.9%) 2
    Oral candidiasis 4/38 (10.5%) 4 0/11 (0%) 0 2/73 (2.7%) 2 1/69 (1.4%) 1
    Oral herpes 2/38 (5.3%) 4 0/11 (0%) 0 2/73 (2.7%) 2 2/69 (2.9%) 2
    Bronchitis 2/38 (5.3%) 2 0/11 (0%) 0 3/73 (4.1%) 3 0/69 (0%) 0
    Folliculitis 5/38 (13.2%) 5 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Candida infection 0/38 (0%) 0 0/11 (0%) 0 4/73 (5.5%) 6 0/69 (0%) 0
    Cellulitis 2/38 (5.3%) 5 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Influenza 0/38 (0%) 0 1/11 (9.1%) 1 2/73 (2.7%) 2 1/69 (1.4%) 1
    Localised infection 3/38 (7.9%) 3 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Pneumonia 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Viral upper respiratory tract infection 1/38 (2.6%) 1 1/11 (9.1%) 2 0/73 (0%) 0 0/69 (0%) 0
    Catheter site cellulitis 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Skin candida 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Injury, poisoning and procedural complications
    Fall 8/38 (21.1%) 14 0/11 (0%) 0 1/73 (1.4%) 1 3/69 (4.3%) 3
    Limb injury 2/38 (5.3%) 2 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Skin abrasion 3/38 (7.9%) 3 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Fibula fracture 0/38 (0%) 0 1/11 (9.1%) 2 0/73 (0%) 0 0/69 (0%) 0
    Procedural pain 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Investigations
    Neutrophil count decreased 3/38 (7.9%) 4 0/11 (0%) 0 13/73 (17.8%) 22 4/69 (5.8%) 5
    Weight decreased 3/38 (7.9%) 3 0/11 (0%) 0 8/73 (11%) 11 2/69 (2.9%) 2
    White blood cell count decreased 1/38 (2.6%) 2 1/11 (9.1%) 6 6/73 (8.2%) 14 1/69 (1.4%) 1
    Aspartate aminotransferase increased 3/38 (7.9%) 3 1/11 (9.1%) 2 1/73 (1.4%) 2 3/69 (4.3%) 4
    Alanine aminotransferase increased 2/38 (5.3%) 3 0/11 (0%) 0 1/73 (1.4%) 2 4/69 (5.8%) 4
    Blood alkaline phosphatase increased 1/38 (2.6%) 1 1/11 (9.1%) 2 2/73 (2.7%) 3 2/69 (2.9%) 3
    Blood pressure increased 0/38 (0%) 0 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Cardiac murmur 2/38 (5.3%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Granulocyte count decreased 0/38 (0%) 0 1/11 (9.1%) 2 0/73 (0%) 0 0/69 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 12/38 (31.6%) 17 2/11 (18.2%) 2 15/73 (20.5%) 18 8/69 (11.6%) 11
    Hypokalaemia 6/38 (15.8%) 8 4/11 (36.4%) 5 13/73 (17.8%) 27 4/69 (5.8%) 5
    Hypomagnesaemia 8/38 (21.1%) 16 3/11 (27.3%) 3 8/73 (11%) 9 7/69 (10.1%) 8
    Dehydration 7/38 (18.4%) 8 0/11 (0%) 0 8/73 (11%) 9 3/69 (4.3%) 4
    Hyperglycaemia 2/38 (5.3%) 3 1/11 (9.1%) 3 2/73 (2.7%) 2 2/69 (2.9%) 3
    Hyponatraemia 1/38 (2.6%) 1 1/11 (9.1%) 1 4/73 (5.5%) 4 1/69 (1.4%) 1
    Hypophosphataemia 2/38 (5.3%) 3 1/11 (9.1%) 1 3/73 (4.1%) 3 0/69 (0%) 0
    Hypocalcaemia 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 2/69 (2.9%) 3
    Hypoalbuminaemia 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Hypercalcaemia 0/38 (0%) 0 1/11 (9.1%) 4 0/73 (0%) 0 0/69 (0%) 0
    Hyperkalaemia 4/38 (10.5%) 4 0/11 (0%) 0 1/73 (1.4%) 2 1/69 (1.4%) 1
    Musculoskeletal and connective tissue disorders
    Myalgia 10/38 (26.3%) 15 2/11 (18.2%) 7 9/73 (12.3%) 11 9/69 (13%) 13
    Arthralgia 11/38 (28.9%) 18 3/11 (27.3%) 3 7/73 (9.6%) 9 6/69 (8.7%) 9
    Pain in extremity 7/38 (18.4%) 14 1/11 (9.1%) 1 8/73 (11%) 9 5/69 (7.2%) 6
    Muscle spasms 3/38 (7.9%) 7 0/11 (0%) 0 4/73 (5.5%) 4 7/69 (10.1%) 9
    Back pain 5/38 (13.2%) 10 1/11 (9.1%) 1 4/73 (5.5%) 4 3/69 (4.3%) 3
    Musculoskeletal pain 2/38 (5.3%) 2 1/11 (9.1%) 1 3/73 (4.1%) 5 2/69 (2.9%) 2
    Neck pain 3/38 (7.9%) 4 0/11 (0%) 0 4/73 (5.5%) 5 1/69 (1.4%) 1
    Muscular weakness 6/38 (15.8%) 9 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 3
    Flank pain 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 3/69 (4.3%) 3
    Bone pain 2/38 (5.3%) 2 0/11 (0%) 0 2/73 (2.7%) 4 1/69 (1.4%) 1
    Musculoskeletal chest pain 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Pain in jaw 3/38 (7.9%) 8 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Musculoskeletal discomfort 2/38 (5.3%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Invasive ductal breast carcinoma 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Nervous system disorders
    Neuropathy peripheral 8/38 (21.1%) 8 4/11 (36.4%) 4 12/73 (16.4%) 15 13/69 (18.8%) 16
    Headache 6/38 (15.8%) 9 1/11 (9.1%) 1 8/73 (11%) 11 13/69 (18.8%) 22
    Dizziness 8/38 (21.1%) 14 0/11 (0%) 0 10/73 (13.7%) 16 6/69 (8.7%) 9
    Peripheral sensory neuropathy 4/38 (10.5%) 4 2/11 (18.2%) 2 9/73 (12.3%) 9 8/69 (11.6%) 9
    Dysgeusia 7/38 (18.4%) 9 0/11 (0%) 0 4/73 (5.5%) 4 5/69 (7.2%) 6
    Somnolence 2/38 (5.3%) 3 1/11 (9.1%) 1 7/73 (9.6%) 9 0/69 (0%) 0
    Paraesthesia 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 5/69 (7.2%) 8
    Restless legs syndrome 3/38 (7.9%) 3 0/11 (0%) 0 3/73 (4.1%) 3 2/69 (2.9%) 2
    Memory impairment 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 2/69 (2.9%) 2
    Amnesia 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 1/69 (1.4%) 1
    Hyperaesthesia 2/38 (5.3%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Tremor 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Product Issues
    Device malfunction 0/38 (0%) 0 1/11 (9.1%) 2 0/73 (0%) 0 0/69 (0%) 0
    Psychiatric disorders
    Insomnia 6/38 (15.8%) 6 2/11 (18.2%) 2 8/73 (11%) 8 7/69 (10.1%) 8
    Anxiety 3/38 (7.9%) 3 1/11 (9.1%) 1 11/73 (15.1%) 11 7/69 (10.1%) 9
    Depression 4/38 (10.5%) 4 1/11 (9.1%) 1 6/73 (8.2%) 7 4/69 (5.8%) 4
    Aggression 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Renal and urinary disorders
    Haematuria 1/38 (2.6%) 1 2/11 (18.2%) 2 3/73 (4.1%) 3 5/69 (7.2%) 5
    Dysuria 2/38 (5.3%) 2 1/11 (9.1%) 1 4/73 (5.5%) 12 3/69 (4.3%) 9
    Pollakiuria 2/38 (5.3%) 2 1/11 (9.1%) 1 3/73 (4.1%) 3 1/69 (1.4%) 1
    Bladder spasm 3/38 (7.9%) 3 0/11 (0%) 0 2/73 (2.7%) 2 0/69 (0%) 0
    Acute kidney injury 2/38 (5.3%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Proteinuria 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Renal failure 2/38 (5.3%) 2 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Cystitis noninfective 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Reproductive system and breast disorders
    Vaginal haemorrhage 3/38 (7.9%) 4 0/11 (0%) 0 0/73 (0%) 0 2/69 (2.9%) 2
    Genital discomfort 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Vulvovaginal pain 3/38 (7.9%) 3 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Cystocele 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Postmenopausal haemorrhage 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 11/38 (28.9%) 13 3/11 (27.3%) 3 17/73 (23.3%) 20 4/69 (5.8%) 4
    Dyspnoea 10/38 (26.3%) 11 3/11 (27.3%) 3 9/73 (12.3%) 10 11/69 (15.9%) 19
    Epistaxis 7/38 (18.4%) 11 1/11 (9.1%) 1 6/73 (8.2%) 6 7/69 (10.1%) 11
    Oropharyngeal pain 10/38 (26.3%) 12 1/11 (9.1%) 1 6/73 (8.2%) 7 2/69 (2.9%) 2
    Nasal congestion 4/38 (10.5%) 5 1/11 (9.1%) 1 3/73 (4.1%) 5 0/69 (0%) 0
    Rhinorrhoea 4/38 (10.5%) 4 1/11 (9.1%) 1 2/73 (2.7%) 2 0/69 (0%) 0
    Pleural effusion 2/38 (5.3%) 2 1/11 (9.1%) 2 2/73 (2.7%) 2 1/69 (1.4%) 1
    Dysphonia 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 1 1/69 (1.4%) 1
    Rhinitis allergic 3/38 (7.9%) 3 0/11 (0%) 0 0/73 (0%) 0 1/69 (1.4%) 2
    Hypoxia 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Pulmonary embolism 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 1/69 (1.4%) 1
    Throat irritation 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Sinus disorder 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 26/38 (68.4%) 29 5/11 (45.5%) 6 28/73 (38.4%) 36 22/69 (31.9%) 24
    Rash 8/38 (21.1%) 9 2/11 (18.2%) 2 5/73 (6.8%) 5 2/69 (2.9%) 2
    Dry skin 4/38 (10.5%) 4 1/11 (9.1%) 1 5/73 (6.8%) 5 2/69 (2.9%) 2
    Pruritus 4/38 (10.5%) 5 0/11 (0%) 0 5/73 (6.8%) 5 2/69 (2.9%) 4
    Erythema 5/38 (13.2%) 6 1/11 (9.1%) 1 2/73 (2.7%) 2 2/69 (2.9%) 4
    Nail disorder 4/38 (10.5%) 4 3/11 (27.3%) 3 1/73 (1.4%) 1 0/69 (0%) 0
    Onycholysis 2/38 (5.3%) 2 0/11 (0%) 0 2/73 (2.7%) 2 3/69 (4.3%) 3
    Skin lesion 6/38 (15.8%) 12 0/11 (0%) 0 1/73 (1.4%) 3 0/69 (0%) 0
    Skin exfoliation 4/38 (10.5%) 4 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Palmar-plantar erythrodysaesthesia syndrome 1/38 (2.6%) 1 1/11 (9.1%) 1 2/73 (2.7%) 2 0/69 (0%) 0
    Pruritus generalised 2/38 (5.3%) 2 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Rash macular 2/38 (5.3%) 2 0/11 (0%) 0 1/73 (1.4%) 4 1/69 (1.4%) 1
    Rash pruritic 3/38 (7.9%) 3 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Nail discolouration 0/38 (0%) 0 1/11 (9.1%) 1 2/73 (2.7%) 2 0/69 (0%) 0
    Rash erythematous 2/38 (5.3%) 3 0/11 (0%) 0 1/73 (1.4%) 1 0/69 (0%) 0
    Dermatitis contact 1/38 (2.6%) 1 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Hyperhidrosis 2/38 (5.3%) 3 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Skin ulcer 2/38 (5.3%) 10 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Solar dermatitis 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Vascular disorders
    Flushing 2/38 (5.3%) 2 1/11 (9.1%) 1 3/73 (4.1%) 5 1/69 (1.4%) 2
    Hot flush 3/38 (7.9%) 4 0/11 (0%) 0 1/73 (1.4%) 1 2/69 (2.9%) 3
    Hypotension 0/38 (0%) 0 0/11 (0%) 0 4/73 (5.5%) 5 2/69 (2.9%) 2
    Deep vein thrombosis 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 1/69 (1.4%) 1
    Lymphoedema 1/38 (2.6%) 1 1/11 (9.1%) 1 1/73 (1.4%) 1 0/69 (0%) 0
    Orthostatic hypotension 3/38 (7.9%) 3 0/11 (0%) 0 0/73 (0%) 0 0/69 (0%) 0
    Blood pressure fluctuation 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0
    Superior vena cava stenosis 0/38 (0%) 0 1/11 (9.1%) 1 0/73 (0%) 0 0/69 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.

    Results Point of Contact

    Name/Title Medical Director
    Organization Takeda
    Phone +1-877-825-3327
    Email trialdisclosures@takeda.com
    Responsible Party:
    Millennium Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01091428
    Other Study ID Numbers:
    • C14008
    • 2009-011428-79
    • U1111-1191-6584
    First Posted:
    Mar 24, 2010
    Last Update Posted:
    Jun 4, 2018
    Last Verified:
    May 1, 2018