- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01512758
A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Tiong Bahru, Singapore, 169610
- National Cancer Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Male or female East Asian participants 18 years or older
- Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas for which no effective standard treatment is available
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Expected survival longer than 3 months from study enrollment
- Radiographically or clinically evaluable tumor
- Female participants who are post menopausal for at least 1 year, surgically sterile, or agree to practice 2 effective methods of contraception through 30 days after the last dose of study drug or agree to abstain from heterosexual intercourse
- Male participants who agree to practice effective barrier contraception through 6 months after the last dose of alisertib or agree to abstain from heterosexual intercourse
- Voluntary written consent
Exclusion Criteria:
- Female participants who are lactating or pregnant
- Treatment with any investigational products, systemic antineoplastic treatment, or antineoplastic treatment with glucocorticoids within 21 days preceding the first dose of alisertib
- Treatment with nitrosoureas, mitomycin C, rituximab, alemtuzumab, or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease)
- Medical conditions requiring daily, chronic, or regular use of proton pump inhibitors or H2-receptor antagonists
- Treatment with radioimmunoconjugates such as ibritumomab tiuxetan or tositumomab within 56 days preceding first alisertib dose
- Major surgery within the 14 days preceding the first dose of alisertib
- Life-threatening or uncontrolled medical illness unrelated to cancer
- Known gastrointestinal (GI) disease or procedures that could interfere with the oral absorption or tolerance of alisertib
- Inability to swallow capsules
- Inadequate bone marrow or other organ function
- Diagnosed or treated for another malignancy within 2 years of first dose of alisertib, or previously diagnosed with another malignancy and have any radiographic or biochemical marker evidence of active disease. In the case of prior prostate cancer treated with radiotherapy, the prostate specific antigen (PSA) may be detectable, but must be < 1 ng/mL. Participants with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy of any type are not excluded
- Other severe acute or chronic medical or psychiatric conditions, including uncontrolled diabetes, or laboratory abnormality
- Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 Names:
|
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 Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Treatment Cycle 1
|
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.
|
First dose to 30 days past last dose (Up to 12.1 Months)
|
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.
|
First dose to 30 days past last dose (Up to 12.1 Months)
|
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.
|
First dose to 30 days past last dose (Up to 12.1 Months)
|
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
|
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
|
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
|
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.
|
Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
|
T1/2: Terminal Half-Life for Alisertib
Time Frame: Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
|
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
|
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
|
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
|
Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline and every 2 cycles for up to 24 months or until progressive disease
|
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.
|
First documented response until disease progression; approximately 12 months
|
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
|
Cycle 1, Day 1; at end of Cycle 2 and every 2 cycles thereafter; and at end treatment; approximately 12 months
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- C14013
- 1015004128 (REGISTRY: TCTIN)
- U1111-1187-6744 (REGISTRY: WHO)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Solid Tumors
-
AmgenCompletedCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced MalignancyUnited States, Australia
-
NantCell, Inc.CompletedQUILT-2.016: Study of AMG 479 With Biologics or Chemotherapy for Subjects With Advanced Solid TumorsCancer | Advanced Solid Tumors | Solid Tumors | Tumors | Advanced Malignancy
-
Incyte CorporationRecruitingA Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid TumorsAdvanced Solid Tumors | Solid Tumors | Metastatic Solid TumorsUnited States, Spain, United Kingdom, France, Italy, Denmark, Switzerland
-
Hoffmann-La RocheCompletedSolid Tumors, Advanced Solid TumorsUnited States
-
Esperance Pharmaceuticals IncCompletedAdvanced Solid Tumors | Solid TumorsUnited States
-
Incyte Biosciences Japan GKCompletedAdvanced Solid Tumors | Metastatic Solid TumorsJapan
-
Memorial Sloan Kettering Cancer CenterKyowa Hakko Kirin Pharma, Inc.CompletedAdvanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Bristol-Myers SquibbCompletedAdvanced Solid Tumors | Metastatic Solid TumorsKorea, Republic of, Canada, Australia
-
Vividion Therapeutics, Inc.RecruitingAdvanced Solid Tumors | Advanced Hematologic TumorsUnited States, Australia
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Solid Tumors, Neoplasms, Advanced SolidHungary
Clinical Trials on Alisertib
-
Millennium Pharmaceuticals, Inc.CompletedOvarian CarcinomaUnited States
-
Millennium Pharmaceuticals, Inc.Completed
-
M.D. Anderson Cancer CenterMillennium Pharmaceuticals, Inc.CompletedLung Cancer | MesotheliomaUnited States
-
The University of Texas Health Science Center at...No longer availableProstate Cancer
-
Millennium Pharmaceuticals, Inc.CompletedSmall Cell Lung Cancer | Non-Small Cell Lung Cancer | Metastatic Breast Cancer | Head and Neck Squamous Cell Carcinoma | Gastroesophageal Adenocarcinoma | Advanced Nonhematological MalignanciesUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedNeuroblastoma | Unspecified Childhood Solid Tumor, Excluding CNS
-
Millennium Pharmaceuticals, Inc.CompletedLymphoma | Advanced Solid TumorsUnited States
-
Millennium Pharmaceuticals, Inc.WithdrawnAdvanced Nonhematologic MalignanciesUnited States
-
Millennium Pharmaceuticals, Inc.CompletedLymphoma | Advanced Solid TumorsUnited States
-
Millennium Pharmaceuticals, Inc.CompletedMultiple Myeloma | Waldenstrom's Macroglobulinemia | Anaplastic Large Cell Lymphoma | Angioimmunoblastic T-cell Lymphoma | Diffuse Large B-cell Lymphoma | B-Cell Chronic Lymphocytic Leukemia | Enteropathy Associated T-cell Lymphoma | B-cell Follicular Lymphoma | B-cell Marginal Zone Lymphoma | B-cell Mantle... and other conditionsUnited States