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A Phase 2 Study of OSI-906 in Patients With Asymptomatic or Mildly Symptomatic (Non-Opioid Requiring) Metastatic Castrate Resistant Prostate Cancer (CRPC)

Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Prostate, Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

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.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the prostate

- Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM);
if the patient is being treated with luteinizing hormone-releasing hormone (LHRH)
agonists (patient who has not undergone orchiectomy), this therapy must have been
initiated at least 4 weeks prior to course 1 Day 1 and must be continued throughout
the study

- Metastatic disease documented by positive bone scan or metastatic lesions other than
liver or visceral metastasis on computed tomography (CT) or magnetic resonance
imaging (MRI); if lymph node metastasis is the only evidence of metastasis, it must
be ≥ 2 cm in diameter

- Prostate cancer progression documented by PSA according to PCWG2 or radiographic
progression according to modified RECIST criteria

- Asymptomatic or mildly symptomatic from prostate cancer; a score of 0-1 on Brief Pain
Inventory (BPI)-Short Form (SF) Question #3 (worst pain in last 24 hours) will be
considered asymptomatic, and a score of 2-3 will be considered mildly symptomatic

- Patients who received combined androgen blockade or received second-line
anti-androgen in the context of CRPC must have shown PSA progression after
discontinuing the anti-androgen prior to enrollment (≥ 4 weeks since last flutamide,
≥ 6 weeks since last bicalutamide or nilutamide) and have progressive disease

- No patients with known brain metastases

- Understand and voluntarily sign an informed consent form

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

- Hemoglobin ≥ 10.0 g/dL independent of transfusion

- Absolute neutrophil count ≥ 1,500/mcL

- Platelet count ≥ 100,000/μL

- Serum albumin ≥ 3.5 g/dL

- Serum creatinine < 1.5 times upper limit of normal (ULN) OR a calculated creatinine
clearance ≥ 60 mL/min

- Serum potassium ≥ 3.5 mmol/L

- Serum bilirubin < 1.5 times ULN (except for patients with documented Gilbert's

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times ULN

- Able to swallow the study drug

- Life expectancy of at least 6 months

- Men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of study participation

- No history of clinically significant heart disease as evidenced by myocardial
infarction or arterial thrombotic events in the past 6 months, severe or unstable
angina, New York Heart Association (NYHA) Class II-IV heart disease, or cardiac
ejection fraction measurement of < 50% at baseline

- No prolonged QTc > 470 msec (mean QTc with Bazett's correction) or history of
familial long QT syndrome

- No other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of
recurrence within 24 months

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to OSI-906

- No uncontrolled intercurrent illness including, but not limited to, psychiatric
illness/social situations that would limit compliance with study requirements

- Patients with insulin-dependent diabetes are excluded

- Patients with known history of HIV on combination antiretroviral therapy are

- Patients with known infectious hepatitis A, B, or C are ineligible

- No condition that, in the opinion of the investigator, would preclude participation
in this trial

- See Disease Characteristics

- Prior therapy with ketoconazole and steroids is allowed provided patients have been
off treatment for 4 weeks

- Prior investigational agents with novel adrenal inhibitors (i.e., Abiraterone or
TAK700) are allowed provided these agents have been discontinued at least 4 weeks
prior to enrollment

- Prior investigational agents with novel antiandrogens (i.e., MDV 3100) are allowed
provided these agents have been discontinued at least 6 weeks prior to enrollment

- Prior therapy with Sipuleucel-T is allowed provided patients have documented evidence
of disease progression as stated above

- Patients receiving any other hormonal therapy, including any dose of Megestrol
acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA
levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must
discontinue the agent for at least 4 weeks prior to enrollment; progressive disease
(as defined above) must be documented after discontinuation of the hormonal therapy

- Patients on stable doses of bisphosphonates that show subsequent tumor progression
may continue on this medication at the discretion of the treating physician; however,
patients are not allowed to initiate bisphosphonate therapy within 4 weeks prior to
starting therapy or throughout the study

- No prior systemic chemotherapy for CRPC; prior neoadjuvant and adjuvant chemotherapy
are allowed when completed at least 12 months prior to enrollment

- No use of opiate analgesics for cancer-related pain, including codeine and
dextropropoxyphene, currently or anytime within 4 weeks of Cycle 1 Day 1

- No prior use of IGF-1R inhibitors (monoclonal antibody or small molecule)

- No palliative radiation therapy to bone metastasis or radionuclide therapy for
treatment of metastatic CRPC within 4 weeks of Cycle 1 Day 1

- Use of the potent CYP1A2 inhibitors ciprofloxacin and fluvoxamine are prohibited

- Other less potent CYP1A2 inhibitors/inducers are not excluded

- Supplements or complementary medicine/botanicals are not permitted while on protocol
therapy, except for any combination of the following:

- Conventional multivitamin supplements

- Selenium

- Lycopene

- Soy supplements

- The use of concomitant steroids is not allowed unless patients are receiving
physiological replacement disease for documented adrenal insufficiency

- Use of drugs that have a known risk of causing Torsades de Pointes (TdP) are
prohibited within 14 days prior to study enrollment

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

PSA response analyzed using the PCWG2 definition

Outcome Description:

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.

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Jorge Garcia

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Cleveland Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

February 2012

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



Cleveland Clinic Foundation Cleveland, Ohio  44195