Linsitinib in Treating Patients With Asymptomatic or Mildly Symptomatic Metastatic Prostate Cancer

This is an interventional treatment trial for Adenocarcinoma of the Prostate Read More

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 disease)
• 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 ineligible
• 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