Cixutumumab and Temsirolimus in Treating Patients With Metastatic Prostate Cancer
|ClinicalTrials.gov Identifier: NCT01026623|
Recruitment Status : Completed
First Posted : December 4, 2009
Last Update Posted : January 22, 2016
|Condition or disease||Intervention/treatment||Phase|
|Hormone-Resistant Prostate Cancer Prostate Adenocarcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer||Biological: Cixutumumab Other: Diagnostic Laboratory Biomarker Analysis Drug: Temsirolimus||Phase 1 Phase 2|
I. To confirm the safety and tolerability of IMC-A12 (cixutumumab) and temsirolimus using the recommended phase II dose level for advanced solid tumors in chemo-naive patients with metastatic castration-resistant prostate cancer and a rising prostate-specific antigen (PSA). (Phase I) II. To confirm the safety and tolerability of IMC-A12 and temsirolimus given on an every three weeks dosing schedule. (Phase I Extension) II. To determine the tumor response rate and/or composite time to progression (cTTP) for chemotherapy-naive patients with castration-resistant prostate cancer (CRPC) receiving the combination of IMC-A12 and CCI-779 (temsirolimus). (Phase II)
I. To determine the maximal percent decrease in PSA from baseline. II. To determine the change in PSA doubling time (PSADT). III. To determine the time to PSA progression and 6-month progression-free survival (PFS).
IV. To determine the rate of adverse events.
I. To evaluate changes in circulating tumor cell (CTC) numbers with time. II. To evaluate IGF1R and androgen receptor (AR) in CTCs and correlate with response.
III. To evaluate profiling CTCs at the molecular level by polymerase chain reaction (PCR) for prostate cancer-specific genes.
IV. To explore the association between clinical outcomes, administration of therapy, and serial fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) imaging.
V. To correlate fluorine F 18 FMDHT (18-FDHT)-PET imaging findings with outcome measures of response.
VI. To perform tumor biopsies and evaluate biomarkers that may correlate with active feedback and tumor response to therapy, including anti-insulin receptor substrate 1 (IRS-1), anti-IRS-2, phosphorylated (p) protein kinase B (Akt)(S473), p-ribosomal protein S6 kinase (70/S6K), anti-phospho-AKT1 substrate 1 (proline-rich) (PRAS 40), and phosphatase and tensin homolog gene (PTEN) status.
OUTLINE: This is a multicenter study.
Patients receive cixutumumab intravenously (IV) over 60-70 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of Anti-IGF-IR Monoclonal Antibody IMC-A12 Plus mTOR Inhibitor Temsirolimus (CCI-779) in Metastatic Castration-Resistant Prostate Cancer (CRPC)|
|Study Start Date :||October 2009|
|Primary Completion Date :||February 2013|
|Study Completion Date :||February 2013|
Experimental: Treatment (cixutumumab, temsirolimus)
Patients receive cixutumumab IV over 60-70 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Diagnostic Laboratory Biomarker Analysis
Correlative studiesDrug: Temsirolimus
- cTTP [ Time Frame: Up to 4 weeks after completion of study treatment ]Defined as the time from the first day of treatment to the earliest one of the following: tumor progression by RECIST; unequivocal evidence of progression by bone scan (at least two new lesions with confirmation at subsequent imaging); new skeletal events; symptomatic progression; or other clinical events attributable to prostate cancer that necessitate major interventions.
- Tumor response rate [ Time Frame: Up to 4 weeks after completion of study treatment ]Defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) and/or the proportion of patients who achieve a greater than 50% reduction in serum PSA compared to baseline.
- Change in PSA doubling time [ Time Frame: Up to 12 weeks ]Compared using descriptive statistics.
- Duration of effect [ Time Frame: From the time of first dose until the time of progression, assessed up to 4 weeks after completion of study treatment ]Summarized using descriptive statistics.
- Maximal percentage decrease in serum PSA [ Time Frame: From baseline to week 12 ]Summarized using descriptive statistics (eg, mean, standard deviation, median, minimum, maximum).
- Progression-free survival [ Time Frame: From the time of first dose until objective tumor progression or death, assessed up to 4 weeks after completion of study treatment ]Summarized using descriptive statistics. Median PFS over time will be determined using Kaplan Meier method.
- Rate of adverse events according to NCI CTCAE version 4.0 [ Time Frame: Up to 4 weeks after completion of study treatment ]Adverse event summaries will be organized by body system, frequency of occurrence, intensity (ie, severity grade), and causality or attribution.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01026623
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Dana Rathkopf||Memorial Sloan Kettering Cancer Center|