Linsitinib in Treating Patients With Asymptomatic or Mildly Symptomatic Metastatic Prostate Cancer
Condition: Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: linsitinib; laboratory biomarker analysis
Intervention description: Oral Linsitinib 150mg, twice a day, days 1- 28; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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