A Phase 2 Study of OSI-906 in Patients With Asymptomatic or Mildly Symptomatic (Non-Opioid Requiring) Metastatic Castrate Resistant Prostate Cancer (CRPC)
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
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
PSA response analyzed using the PCWG2 definition
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.
The Cleveland Clinic
United States: Food and Drug Administration
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