Linsitinib in Treating Patients With Asymptomatic or Mildly Symptomatic Metastatic Prostate Cancer
This phase II trial studies how well linsitinib works in treating patients with asymptomatic or mild symptomatic metastatic prostate cancer. Linsitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of OSI-906 in Patients With Asymptomatic or Mildly Symptomatic (Non-Opioid Requiring) Metastatic Castrate Resistant Prostate Cancer (CRPC)|
- PSA response analyzed using the PCWG2 definition [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]Measured data will be summarized using means, standard deviations, medians, and ranges. The 95% confidence intervals should also be provided. Waterfall plots will be used.
- Incidence of toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
- RECIST-based response in patients with bidimensional measurable disease [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
- Time to PSA progression analyzed using the PCWG2 definition [ Time Frame: Up to date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, assessed up to 12 weeks ] [ Designated as safety issue: No ]Summarized using the method of Kaplan and Meier.
- Overall survival based on the RECIST v1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]Summarized using the method of Kaplan and Meier.
|Study Start Date:||February 2012|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (linsitinib)
Patients receive linsitinib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo serum and plasma sample collection at baseline, on day 1 of courses 2 and 4, and after completion of study treatment for correlative studies.
Other Name: OSI-906Other: laboratory biomarker analysis
I. To evaluate time to prostate-specific antigen (PSA) progression based on Prostate Cancer Working Group (PCWG2) criteria.
II. To evaluate PSA response (proportion of patients achieving a PSA decline > 50% according to PCWG2 criteria in patients receiving linsitinib [OSI-906]).
III. To evaluate overall response rate (ORR) in patients with Response Evaluation Criteria in Solid Tumors (RECIST)-defined measurable disease receiving OSI-906.
I. To evaluate the effect of OSI-906 on time-to opiate use for cancer pain. II. To evaluate the effect of OSI-906 on radiographic progression-free survival (rPFS) of patients with asymptomatic or mildly symptomatic (non-opioid requiring) castrate-resistant prostate cancer (CRPC).
III. To evaluate the overall survival (OS) of patients with asymptomatic or mildly symptomatic (non-opioid requiring) CRPC receiving OSI-906.
IV. To further evaluate the safety of OSI-906 in patients with asymptomatic or mildly symptomatic (non-opioid requiring) CRPC.
I. To describe the effects of OSI-906 in the levels of androstenedione, dehydroepiandrostenedione (DHEA), DHEA-sulfate, p insulin-like growth factor-1 receptor (IGF-IR), and p-insulin receptor (IR). (Exploratory) II. To describe the effects of OSI-906 in the levels of transforming growth factor (TGF)-beta (b1), interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha (a), and monocyte chemotactic protein 1 (MCP-1) as markers of metastatic progression. (Exploratory) III. To describe the effects of OSI-906 on the number of circulating tumor cells (CTCs) and endothelial cells (CECs). (Exploratory) IV. To use ribonucleic acid (RNA) extracted from CTCs to evaluate effects on downstream targets of IGF-1R signaling after OSI-906 treatment. (Exploratory) V. To measure the effect of OSI-906 on the expression of IGF-1R on CTCs. (Exploratory)
Patients receive linsitinib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo serum and plasma sample collection at baseline, on day 1 of courses 2 and 4, and after completion of study treatment for correlative studies.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01533246
|United States, Ohio|
|Case Western Reserve University|
|Cleveland, Ohio, United States, 44106|
|Cleveland Clinic Foundation|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Jorge Garcia||The Cleveland Clinic|