Symptoms and General Pathology

All Conditions

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Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Digestive System Diseases

Rare Diseases

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Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Fallopian Tube Neoplasms

Peritoneal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

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Urogenital Neoplasms

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Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Abdominal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Peritoneal Diseases

Ovarian Cancer

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Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

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).

Alisertib

Medical Monitor

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).

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.

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

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

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.

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).

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.

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.

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

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.

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).

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.

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.

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

Millennium Pharmaceuticals, Inc.

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.

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 (Phase 1 - Ovarian Cancer)

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 (Phase 1 - Breast Cancer)

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

Paclitaxel 80 mg/m^2 (Phase 2)

Total

Age, Continuous

Sex: Female, Male

Hispanic or Latino

Not Hispanic or Latino

Not Reported

Missing

Race/Ethnicity, Customized

White

Black or African American

Asian

American Indian or Alaskan Native

Other

United States

Poland

France

Region of Enrollment

Height data was only available for 72 participants in the Alisertib 40 mg BID+ Paclitaxel 60 mg/m\^2 arm in Phase 2.

Height

Weight

Body Surface Area (m\^2) = square root \[height (cm) x weight (kg) / 3600\].

Body Surface Area was only calculated for 72 participants in the Alisertib 40 mg BID + Paclitaxel 60 mg/m\^2 arm in Phase 2.

Body Surface Area

Safety population was defined as all participants who received at least 1 dose of any study drug.

Medical Director

Alisertib + Paclitaxel (Phase 1)

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.

Phase 1: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) for Alisertib in Combination With Paclitaxel

Paclitaxel 60 or 80 mg/m\^2, intravenous infusion, weekly (Days 1, 8, 15) in 28-day cycles in Phase 1.

Alisertib + Paclitaxel

Phase 1: MTD and RP2D for Paclitaxel in Combination With Alisertib

SAEs

Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Neutrophil count decreased

White blood cell count decreased

Aspartate aminotransferase increased

Alanine aminotransferase increased

Ammonia increased

Transaminases increased

Blood alkaline phosphatase increased

High density lipoprotein decreased

Urine output decreased

Granulocyte count decreased

Phase 1: Number of Participants With Clinically Significant Laboratory Values

Pyrexia

Heart rate irregular

Blood pressure increased

Weight decreased

Phase 1: Number of Participants With Clinically Significant Vital Sign Findings

Hypersensitivity

Neurotoxicity

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.

Phase 1: Number of Participants With Hypersensitivity and Neurotoxicity

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

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.

Phase 2: Progression-Free Survival (PFS)

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.

Phase 1: Combined Best Overall Response Rate (ORR) in Participants With Recurrent Ovarian Cancer or Breast Cancer

Cycle1 (Day1)

Cycle1 (Day3)

Alisertib 10 mg BID + Paclitaxel 80 mg/m^2

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

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 20 mg BID + Paclitaxel 60 mg/m^2

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 30 mg BID + Paclitaxel 60 mg/m^2

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 40 mg BID + Paclitaxel 60 mg/m^2

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 50 mg BID + Paclitaxel 60 mg/m^2

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.

Cmax: Maximum Observed Concentration for Alisertib in Phase 1

Cycle 1, Day 1

Cycle 1, Day 3

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.

Tmax: Time to First Occurrence of Cmax for Alisertib in Phase 1

Cycle 1, Day3

AUC(Tau): Area Under the Concentration-Time Curve During a Dosing Interval for Alisertib in Phase 1

AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib in Phase 1

Cycle 2, Day 1

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.

Cmax: Maximum Observed Concentration for Paclitaxel in Phase 1

AUClast: Area Under the Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Paclitaxel in Phase 1

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

t½: Terminal Half-Life for Paclitaxel in Phase 1

CL: Total Clearance After Intravenous Administration, Calculated Using the Observed Value of the Last Quantifiable Concentration for Paclitaxel in Phase 1

Vss: Volume of Distribution at Steady State for Paclitaxel in Phase 1

Vz: Volume of Distribution During the Terminal Disposition Phase for Paclitaxel in Phase 1

Phase 2: Combined Best Overall Response Rate (ORR)

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.

Phase 2: Duration of Response (DOR)

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

Phase 2: Time to Disease Progression (TTP)

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.

Phase 2: Overall Survival (OS)

Phase 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Lymphocyte count decreased

Gamma-glutamyltransferase increased

Haemoglobin decreased

Blood magnesium decreased

Blood creatinine increased

Platelet count decreased

International normalised ratio increased

Blood albumin decreased

Troponin T increased

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

Phase 2: Number of Participants With Clinically Significant Laboratory Values

Heart rate increased

Phase 2: Number of Participants With Clinically Significant Vital Sign Findings

This Outcome Measure was originally registered as a Secondary but this Outcome Measure was Exploratory and no data was collected.

Spots Global Cancer Trial Database for recist: response evaluation criteria in solid tumors