This phase I/II trial is studying the side effects of giving cixutumumab together with temsirolimus and to see how well it works in treating patients with metastatic prostate cancer. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab together with temsirolimus may kill more tumor cells.
PRIMARY OBJECTIVES: 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) SECONDARY OBJECTIVES: 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. EXPLORATORY OBJECTIVES: 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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
cTTP
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. This Outcome Measure is related to the Phase II portion of the Trial, which did not occur. Therefore, there is no data to report.
Time frame: Up to 4 weeks after completion of study treatment
Tumor Response Rate
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.
Time frame: Up to 4 weeks after completion of study treatment
Change in PSA Doubling Time
Compared using descriptive statistics. PSA doubling time is defined as the number of months it would take for PSA to increase two-fold. PSADT is inversely proportional to the slope of the regression line for the relation between log PSA and time. If this slope is negative, so the patient's PSA is going down over time, then the PSADT is negative.
Time frame: Week 1, Week 5, Week 9, Week 13, Week 17, Week 21 and Week 25
Duration of Effect
Summarized using descriptive statistics.
Time frame: From the time of first dose until the time of progression, assessed up to 4 weeks after completion of study treatment
Maximal Percentage Change in Serum PSA as Compared to Week 12 Versus Baseline
Summarized using descriptive statistics (eg, mean, standard deviation, median, minimum, maximum). Maximum percent change in serum PSA (i.e., 100%\*\[(value at Week 12 minus value at baseline)/value at baseline\])
Time frame: From baseline to week 12
Progression-free Survival
Summarized using descriptive statistics. Median PFS over time will be determined using Kaplan Meier method. This Outcome Measure was related to the Phase 2 portion of the study, which did not occur. Therefore, there is no data to report.
Time frame: From the time of first dose until objective tumor progression or death, assessed up to 4 weeks after completion of study treatment
Rate of Adverse Events According to NCI CTCAE Version 4.0
Adverse event summaries will be organized by body system, frequency of occurrence, intensity (ie, severity grade), and causality or attribution. Please see Adverse Event/Serious Adverse Event Section.
Time frame: Up to 4 weeks after completion of study treatment
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