Alisertib in Treating Patients With Advanced or Metastatic Sarcoma
|ClinicalTrials.gov Identifier: NCT01653028|
Recruitment Status : Completed
First Posted : July 30, 2012
Results First Posted : December 28, 2016
Last Update Posted : November 30, 2017
|Condition or disease||Intervention/treatment||Phase|
|Myxofibrosarcoma Recurrent Adult Soft Tissue Sarcoma Recurrent Leiomyosarcoma Recurrent Liposarcoma Recurrent Malignant Peripheral Nerve Sheath Tumor Recurrent Undifferentiated Pleomorphic Sarcoma Stage III Soft Tissue Sarcoma AJCC v7 Stage IV Soft Tissue Sarcoma AJCC v7||Drug: Alisertib Other: Laboratory Biomarker Analysis||Phase 2|
I. To determine the response rate (complete response [CR] + partial response [PR]) assessed for patients within each cohort: liposarcoma (cohort 1); leiomyosarcoma (non-uterine) (cohort 2); undifferentiated sarcoma (including pleomorphic undifferentiated sarcoma, formerly known as malignant fibrous histiocytoma, and myxofibrosarcoma) (cohort 3); malignant peripheral nerve sheath tumor (cohort 4); and other sarcomas (cohort 5).
I. To estimate the progression-free survival (PFS) and overall survival (OS) for patients treated with MLN8237 (alisertib) in each cohort.
II. To assess the adverse events associated with patients treated with MLN8237 in each cohort.
I. To correlate potential clinical benefit with markers of aurora kinase inhibition in pre- and post-treatment tumor biopsies.
II. To correlate clinical outcome with change in fluorine F 18 fluorothymidine (FLT)-positron emission tomography (PET) uptake at baseline versus after one week of treatment (ie, week 2 of cycle 1).
Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for 18 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||72 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of MLN8237 in Advanced/Metastatic Sarcoma|
|Actual Study Start Date :||August 22, 2012|
|Actual Primary Completion Date :||August 2, 2015|
Experimental: Treatment (alisertib)
Patients receive alisertib PO BID on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- The Primary Endpoint for This Trial Was the Percent of Confirmed Tumor Responses. Confirmed Tumor Response to Treatment Was Defined as a Complete or Partial Response(Per RECIST 1.1) on Two Consecutive Evaluations at Least 6 Weeks Apart. [ Time Frame: Up to 18 months ]The primary endpoint was estimated by the number of confirmed responses divided by the total number of evaluable patients per cohort. The study used a two stage Simon design to assess the primary endpoint. A confirmed tumor response rate of 5% was considered not promising; an observed confirmed response rate of 25% was considered promising. One confirmed response within the initial 9 patients enrolled within each cohort, expanded enrollment to 24 patients in that cohort. 3 out of 24 patients with confirmed tumor responses was considered evidence that this treatment could be recommended for further testing. This study design yielded 90% power to detect a true confirmed response rate of at least 25% at .10 level of significance if the true rate is at most 5%. There was a 63% chance of stopping early if the true confirmed response rate was 5%.
- Overall Survival (OS) [ Time Frame: The time between registration and death, assessed up to 18 months ]The distribution will be estimated by the methods of Kaplan and Meier. The estimates of survival at specific time points will be calculated (eg, median, 6 month survival).
- Progression Free Survival (PFS) [ Time Frame: The time between registration to disease progression or death, assessed up to 18 months ]The distribution will be estimated by the methods of Kaplan and Meier. The estimates of PFS at specific time points will be calculated (eg, median, 1 year PFS).
- Adverse Events [ Time Frame: During treatment and up to 5 years ]Adverse Events: Incidence of adverse events, assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Adverse events were collected every cycle during treatment and up to one month after treatment. Adverse events were summarized using summary statistics and frequency tables for each separate cohort. Per protocol, analysis was descriptive in nature. In this section, the number of patients that reported a grade 4 or higher event are summarized. A complete listing of Adverse Events is provided in the Adverse Events section below.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01653028
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|Principal Investigator:||Mark Dickson||Alliance for Clinical Trials in Oncology|