A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas
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|ClinicalTrials.gov Identifier: NCT01512758|
Recruitment Status : Completed
First Posted : January 19, 2012
Results First Posted : March 15, 2019
Last Update Posted : March 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors Lymphomas||Drug: Alisertib||Phase 1|
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have advanced solid tumors or lymphomas for which standard curative or life-prolonging treatment did not exist or was no longer effective or tolerable. This study evaluated the safety and pharmacokinetic (PK) profile, and maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of alisertib, as well as any antitumor activity.
The study enrolled 36 patients. Participants were assigned to one of the two treatment groups and received:
- Alisertib 30 mg
- Alisertib 40 mg All participants took two enteric-coated tablets every 12 hours each day for 7 days followed by a 14-day rest period in a 21-day cycle for up to 16 cycles.
This multi-center trial is conducted in East Asia. The overall time to participate in this study was 24 months, unless it was determined that a participant would derive benefit from continued therapy beyond 24 months. Participants made multiple visits to the clinic, and were contacted up to a maximum of 30 days after last dose of study drug for a follow-up assessment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Dose Escalation and Pharmacokinetic Study of Alisertib (MLN8237), an Aurora A Kinase Inhibitor, in Adult East Asian Patients With Advanced Solid Tumors or Lymphomas|
|Actual Study Start Date :||February 6, 2012|
|Actual Primary Completion Date :||October 8, 2013|
|Actual Study Completion Date :||October 8, 2013|
Experimental: Alisertib 30 mg
Alisertib 30 mg enteric-coated tablets (ECT), orally, twice a day (BID) for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 16 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib enteric-coated tablets
Other Name: MLN8237
Experimental: Alisertib 40 mg
Alisertib 40 mg ECT, orally, BID for 7 days, followed by a 14-day rest period, in 21-day cycles until there is evidence of disease progression or unacceptable alisertib-related toxicities (up to 7 cycles). Cycles could be extended to 28-day cycles (with additional 7-day rest period) if all alisertib-related toxicities (except alopecia) were not resolved to less than Grade 2.
Alisertib enteric-coated tablets
Other Name: MLN8237
- Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [ Time Frame: Treatment Cycle 1 ]MTD was defined as highest dose at which <2 participants experienced a dose-limiting toxicity (DLT). DLT was defined as any of the following events considered possibly related to therapy with alisertib by the investigator: 1. Grade 4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >7 days; 2. Grade 4 neutropenia with fever (oral or ear temperature ≥38.5°C); 3. Grade 4 thrombocytopenia (platelets <25,000/mm^3) for >7 days; 4. Platelet count <10,000 cells/mm^3; 5. ≥Grade 3 thrombocytopenia with clinically significant bleeding; 6. Delay in initiation of subsequent cycle by >7 days due to treatment-related toxicity; 7. ≥Grade 3 nonhematological toxicity except following: a. ≥Grade 3 nausea and/or emesis in the absence of optimal antiemetic therapy; b. ≥Grade 3 diarrhea in the absence of optimal supportive therapy; c. Grade 3 fatigue lasting <1 week; d. Other Grade 3 nonhematological toxicity that can be safely and reliably controlled to ≤Grade 2 with appropriate treatment.
- Number of Participants With Adverse Events and Serious Adverse Events [ Time Frame: First dose to 30 days past last dose (Up to 12.1 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.
- Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events [ Time Frame: First dose to 30 days past last dose (Up to 12.1 Months) ]Laboratory AEs in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, investigations, and metabolism and nutrition disorders. An abnormal laboratory value was assessed as an AE if that value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment¬-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events [ Time Frame: First dose to 30 days past last dose (Up to 12.1 Months) ]Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.
- Cmax: Maximum Observed Concentration for Alisertib [ Time Frame: Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose ]
- Tmax: Time to First Occurrence of Cmax for Alisertib [ Time Frame: Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose ]
- AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval (τ) for Alisertib [ Time Frame: Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose ]
- Dose Normalized AUCτ: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib [ Time Frame: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose ]Dose normalized AUCτ was obtained using AUCτ divided by alisertib dose in milligrams.
- T1/2: Terminal Half-Life for Alisertib [ Time Frame: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose ]
- Rac: Accumulation Ratio for Alisertib [ Time Frame: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose ]
- PTR: Peak Trough Ratio During a Dosing Interval, at Steady State for Alisertib [ Time Frame: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose ]
- CLss/F: Apparent Clearance After Extravascular Administration, at Steady State, Calculated Using AUCτ for Alisertib [ Time Frame: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose ]
- Best Overall Response Rate Based on Investigator Assessment [ Time Frame: Baseline and every 2 cycles for up to 24 months or until progressive disease ]Best overall response rate is defined as the percentage of participants with complete response (CR) and/or partial response (PR) as assessed by the Investigator using Lymphoma International Working Group (IWG) Criteria or Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT, PET or MRI. IWG criteria for CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. RECIST response criteria is defined as: 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.
- Duration of Response [ Time Frame: First documented response until disease progression; approximately 12 months ]DOR is defined as the time from the date of first documentation of a CR response to the date of first documentation of PD according to IWG criteria or RECIST criteria 1.1. IWG PD is defined as PD is defined as any new lesion or increase by >50% of previously involved sites from nadir. RECIST PD is defined as unequivocal progression of existing non-target lesions.
- Concentrations of Relevant Tumor Markers [ Time Frame: Cycle 1, Day 1; at end of Cycle 2 and every 2 cycles thereafter; and at end treatment; approximately 12 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01512758
|National Cancer Centre|
|Tiong Bahru, Singapore, 169610|
|Study Director:||Medical Director Clinical Science||Millennium Pharmaceuticals, Inc.|