Cixutumumab and Temsirolimus in Treating Patients With Locally Recurrent or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00699491|
Recruitment Status : Completed
First Posted : June 18, 2008
Results First Posted : May 21, 2015
Last Update Posted : June 13, 2018
|Condition or disease||Intervention/treatment||Phase|
|Male Breast Carcinoma Recurrent Breast Carcinoma Stage IV Breast Cancer AJCC v6 and v7||Biological: Cixutumumab Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Temsirolimus||Phase 1 Phase 2|
I. To establish the recommended dose level for the phase II trial. (Phase I) II. To examine the safety profile of this combination in patients with metastatic breast cancer. (Phase I) III. To assess the anti-tumor activity (in terms of overall response rate) and toxicity profile of IMC-A12 (cixutumumab) in combination with temsirolimus in patients with metastatic breast cancer. (Phase II)
I. To estimate the progression-free survival (PFS) and overall survival distributions (as well as the 6-month PFS rate).
II. To evaluate the in vivo mechanisms of action of temsirolimus in combination with IMC-A12 and to examine potential biomarker predictors of treatment response.
OUTLINE: This is a phase I, dose-escalation study of cixutumumab followed by a phase II study.
Patients receive temsirolimus intravenously (IV) over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22 (cixutumumab is given on days 8, 15, and 22 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 2 (phase I) or 5 (phase II) years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of IMC-A12 in Combination With Temsirolimus in Patients With Metastatic Breast Cancer|
|Actual Study Start Date :||October 31, 2008|
|Actual Primary Completion Date :||September 9, 2013|
|Actual Study Completion Date :||February 14, 2018|
Experimental: Treatment (cixutumumab, temsirolimus)
Patients receive temsirolimus IV over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22 (cixutumumab is given on days 8, 15, and 22 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Recommended Dose Level for Phase II Testing (RPTD) (Phase I) [ Time Frame: During first course ]
The RPTD is defined as the highest dose level at which at most one of 6 patients develops a dose limiting toxicity (DLT) during the first course of treatment and the next highest dose level has 2 or more DLTs. The number of patients in each cohort reporting a DLT is reported.
Dose-limiting toxicities (DLTs) are defined as any of the following adverse events (AEs) that are related to study agent with an attribution of possible, probably, or definite and fulfilling one of the following criteria:
- Any grade 4 hematologic toxicity
- Hyperglycemia that cannot be stably controlled with diabetic medication
- Any grade 3 or 4 non-hematologic toxicity (except asymptomatic medically manageable laboratory abnormalities such as hyperlipidemia, hypophosphatemia, and hypokalemia)
- Tumor Response Rate (TRR) (Complete Response [CR] or Partial Response [PR]) by the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II) [ Time Frame: Up to 5 years ]
A response is defined as a disease burden that meets the RECIST criteria for Complete Response (CR) or Partial Response (PR) on 2 consecutive evaluations at least 6-8 weeks apart.
Complete Response (CR): All of the following must be true:
- Disappearance of all target and non-target lesions.
- Each target lymph node must have reduction in short axis to <1.0 cm.
Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline measures.
The rate is calculated by dividing the number of patients with a CR or PR by the number of evaluable patients. A ninety percent confidence interval for the true tumor response rate will be calculated using the Duffy-Santer approach.
- Adverse Events Graded Using the NCI CTCAE Version. 3 (Phase II) [ Time Frame: Up to 5 years ]Adverse events will be graded using the NCI-CTCAE v3.0 coding scheme. The maximum grade for each adverse event considered to be 'at least possibly related to treatment' will be recorded. Frequency tables will be constructed and the number of patients reporting an adverse event of grade 3 or higher at least possibly related to treatment will be reported.
- Duration of Response (Phase II) [ Time Frame: Up to 5 years ]Duration of response is defined for all evaluable patients with changes in disease burden that met the RECIST criteria for CR or PR on 2 consecutive evaluations at least 6-8 weeks apart as the date at which the CR or PR to the date progression is documented. The distribution of response durations will be estimated using the Kaplan-Meier method.
- Progression Free Survival (PFS) (Phase II) [ Time Frame: Time from registration to documentation of disease progression, up to 5 years ]Progression free survival is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. If the patient is declared to be a major treatment violation, the patient will be censored on the date the treatment violation was declared to have occurred. In the case of a patient starting treatment and then never returning for any evaluations, the patient will be censored for progression on the last day of therapy was administered. The distribution of progression-free survival times will be estimated using the Kaplan-Meier method.The distribution of PFS times will be estimated using the Kaplan-Meier method.
- Progression Free Survival Rate [ Time Frame: At 6 months ]Progression free survival (PFS) is defined as the time from registration to documentation of disease progression. A point and interval estimate of the 6 month PFS rate will be obtained using the Kaplan-Meier method.
- Survival Time (Phase II) [ Time Frame: Time from registration to death due to any cause ]Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
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): NCT00699491
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|Principal Investigator:||Cynthia Ma||Alliance for Clinical Trials in Oncology|