The purpose of this study is to evaluate the safety and tolerability and determine the MTD to subsequently define an RP2D of alisertib in combination with weekly paclitaxel in East Asian participants with advanced solid tumors.
The drug being tested in this study was called alisertib. Alisertib in combination with paclitaxel was tested to find a safe and well-tolerated dose in East Asian participants. The study consisted of 2 parts: a dose escalation phase to determine the maximum tolerated dose (MTD) and define the recommended phase 2 dose (RP2D) of the alisertib plus paclitaxel combination in East Asian participants with advanced solid tumors; the second part is an expansion cohort at the RP2D of the alisertib plus paclitaxel in East Asian participants with either ovarian cancer or small cell lung cancer. This study looked at safety (lab results and side effects) and pharmacokinetic properties (how the drugs move throughout the body). This open label study enrolled 9 participants. Dose Escalation Phase: Alisertib tablets at a starting dose of 15 mg, orally, twice daily, 3 days on/4 days off for 3 weeks in 28 day cycle in combination with paclitaxel, 60 mg/m\^2 intravenous on days 1, 8, and 15 in 28-day cycles in Cohort 1 escalated to a dose of 25 mg alisertib, orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in Cohort 2. If ≥ 2 participants experience a dose limiting toxicity (DLT) the dose of alisertib decreased to 20 mg. Expansion Cohort: alisertib tablets at the determined RP2D dose orally, twice daily 3 days on/4 days off for 3 weeks in 28 day cycles in combination with paclitaxel, 60 mg/m\^2 intravenous. Treatment was continued until disease progression or unacceptable toxicity. * Alisertib 15 mg to 25 mg tablets * Paclitaxel 60 mg/m\^2 intravenous solution This multi-centre trial was conducted in Japan and Korea. The overall time to participate in this study was up to 24 months. The study was terminated early because of the sponsor's decision. Enrollment was completed in the dose escalation cohort, but no participants were enrolled in the dose expansion cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Alisertib tablets
Paclitaxel intravenous solution
Unnamed facility
Chiba, Japan
Unnamed facility
Shizuoka, Japan
Unnamed facility
Seoul, South Korea
Dose Escalation Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Dose Escalation Phase: Number of Participants With Clinically Significant Laboratory Findings
The number of participants with any markedly abnormal standard safety laboratory values including serum chemistry, hematology, and urine analysis will be collected throughout study. Laboratory values assessed by the investigator to be clinically significant were reported as adverse events.
Time frame: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Dose Escalation Phase: Number of Participants With Clinically Significant Vital Sign Findings
The number of participants with any markedly abnormal vital sign values (blood pressure, heart rate, and temperature) will be collected throughout study. Vital signs assessed by the investigator to be clinically significant were reported as adverse events.
Time frame: From Day 1 to 30 days after the last dose of study drug (approximately 21 months)
Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
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Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2 and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Tme 0 to Infinity
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Escalation Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE 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: From Day 1 to 30 days after the last dose of study drug
Dose Expansion Phase: Number of Participants With Clinically Significant Laboratory Findings
The number of participants with any markedly abnormal standard safety laboratory values will be collected throughout study.
Time frame: From Day 1 to 30 days after the last dose of study drug
Dose Expansion Phase: Number of Participants With Clinically Significant Vital Sign Findings
The number of participants with any markedly abnormal vital sign values will be collected throughout study.
Time frame: From Day 1 to 30 days after the last dose of study drug
Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for Alisertib
Time frame: Day 1 and Day 3 predose and at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Cmax: Maximum Observed Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Tmax: Time to Reach the Maximum Plasma Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-tlast): Area Under the Plasma Concentration Curve From Time Zero to the Time of the Last Quantifiable Concentration of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: AUC(0-inf): Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: T½: Terminal Phase Elimination Half-Life of Paclitaxel
Time frame: Day 1 predose and Day 1, 2, and 3 at multiple time points (up to 12 hours) post-dose
Dose Expansion Phase: Overall Response Rate (ORR)
ORR is defined as the percentage of participants with complete response (CR) and partial response (PR) according to disease response based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: Day 21 of every other Cycle beginning with Cycle 2 (Up to 12 months)