Tivantinib in Treating Patients With Metastatic Prostate Cancer
Condition: Hormone-Resistant Prostate Cancer; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Laboratory Biomarker Analysis; Placebo; Tivantinib
Intervention description: Optional correlative studies; Given PO; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 78.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well tivantinib works compared to placebo in
      treating patients with metastatic prostate cancer. Tivantinib may stop the growth of tumor
      cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically documented adenocarcinoma of the prostate with
             progressive systemic disease (either rising PSA or progression of disease on CT scan
             or magnetic resonance imaging [MRI] or bone scan) despite castrate levels of
             testosterone due to orchiectomy or luteinizing hormone-releasing hormone (LHRH)
             agonist or antagonist; castrate levels of testosterone must be maintained throughout
             the study

          -  Evidence of metastatic disease on CT or bone imaging

          -  Patients must have demonstrated evidence of progressive disease since the most recent
             change in therapy; progressive disease is defined as any one of the following
             (measurable disease, bone scan, or PSA progression):

               -  Measurable disease progression: objective evidence of increase > 20% in the sum
                  of the longest diameters (LD) of target lesions from the time of maximal
                  regression or the appearance of one or more new lesions

               -  Bone scan progression: appearance of two or more new lesions on bone scan
                  attributable to prostate cancer will constitute progression

               -  PSA progression: two successive rises from baseline PSA separated at least by one
                  week with the last value >= 2 ng/mL

          -  Asymptomatic or minimally symptomatic from prostate cancer - no symptoms attributed to
             prostate cancer greater than grade I using NCI CTCAE version 4.0 grading of toxicities

          -  Secondary hormonal therapies (e.g., abiraterone acetate, flutamide, estrogen) must be
             discontinued for at least 4 weeks prior to study enrollment unless the duration of the
             therapy was less than 8 weeks and there was no demonstrated decrease in PSA

          -  Secondary hormonal therapies with bicalutamide or nilutamide must be discontinued for
             6 weeks unless duration of therapy was less than 8 weeks and there was no demonstrated
             PSA decrease

          -  Prior abiraterone (or investigational anti-androgen) use is allowed; these too will
             need to be discontinued at least 4 weeks prior to study enrollment

          -  PSA prior to treatment must be >= 2 ng/ml

          -  Castrate testosterone level (< 50 ng/dL)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  No prior chemotherapy unless utilized in neoadjuvant/adjuvant setting and must have
             completed > 6 months prior to enrollment

          -  Four weeks since major surgery or radiation therapy

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.0 X institutional upper limit of normal

          -  Creatinine within normal institutional limits OR creatinine clearance >= 40
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Patients must have signed an informed consent document stating that they understand
             the investigational nature of the proposed treatment

          -  Men and any female partners of child-bearing potential must agree to use adequate
             contraception (hormonal or barrier method of birth control) prior to study entry and
             for the duration of study participation and for additional 2 months after finishing
             therapy; should a patient's sexual partner become pregnant or suspect she is pregnant
             while patient is participating in this study, he should inform the treating physician
             immediately

          -  Bisphosphonate or denosumab therapy is permitted provided patients began therapy prior
             to registration and that they continue them as per the manufacturer's guidelines
             and/or per institutional practice; patients not taking ongoing bisphosphonate or
             denosumab therapy will not be permitted to start such therapy until they have
             completed 12 weeks of study treatment

          -  Patients must be able to swallow pills to participate in the study

        Exclusion Criteria:

          -  Patients who have radiotherapy within 4 weeks or chemotherapy prior to entering the
             study or those who have not recovered (resolution to grade 1) from adverse events due
             to agents administered more than 4 weeks earlier; neoadjuvant/adjuvant chemotherapy
             for local disease is allowed if greater than 6 months have elapsed

          -  Previous hepatocyte growth factor receptor (C-MET) inhibitor treatment (either
             monoclonal antibody to C-MET or human growth factor [HGF] or small molecule inhibitory
             to C-MET)

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition ARQ 197

          -  Caution should be used with patients receiving inhibitors of cytochrome P450 family 2,
             subfamily C, polypeptide 19 (CYP2C19) and strong inhibitors of cytochrome P450 family
             3, subfamily A, polypeptide4 (CYP3A4); additional hematologic testing will be advised
             if the medication cannot be substituted

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or known psychiatric illness/social situations that would limit compliance
             with study requirements

          -  Known brain metastasis

          -  Current, recent (within 4 weeks of the first study drug administration), or concurrent
             planned participation in another investigational therapeutic study

          -  Patients with a "currently active" second malignancy other than non-melanoma skin
             cancers are not to be registered; patients are not considered to have a "currently
             active" malignancy if they have completed therapy and are now considered to be at less
             than 30% risk for relapse (by their physician)

          -  Patients may continue on a daily multi-vitamin and calcium/vitamin D supplements; all
             other herbal, alternative, and food supplements (i.e., PC-SPES, Saw Palmetto, St. John
             wort, etc.) must be discontinued before registration

          -  New York Heart Association (NYHA) class III or greater congestive heart failure

          -  History of myocardial infarction or unstable angina within 6 months prior to initial
             treatment

          -  History of severely impaired lung function

          -  Baseline electrocardiogram (ECG) abnormalities including first degree (PR interval >
             210 ms), second degree, or third degree heart block (exception: patients with
             pacemakers may be enrolled); QRS prolongation or bundle branch block (QRS >= 120 ms),
             or QT prolongation (per institutional standard of care: Fridericia corrected QT
             interval [QTcF] or Bazett corrected QT interval [QTcB] >= 470 ms); other ECG
             abnormalities will need consideration by the treating investigator and enrollment is
             up to his/her discretion

          -  Presence of non-healing wound, active ulcer, or untreated bone fracture

          -  Known diabetics that have poorly controlled diabetes mellitus (glycated hemoglobin
             [HbA1c] >= 8.0%) or fasting glucose level >= 189 mg/dL (diabetic patient); patients
             may be potentially eligible once anti-diabetic agent(s) are either added or titrated
             to control their diabetes mellitus

          -  Active liver disease (AST or ALT >= 2.0 times the upper limit of normal [ULN] or total
             bilirubin >= institutional ULN) or gallbladder disease; patients with known liver
             cirrhosis or severe hepatic impairment (Child-Pugh Class C) will also be excluded

          -  A known history of human immunodeficiency virus (HIV) seropositivity

          -  Impairment of gastrointestinal function or gastrointestinal disease that may
             significantly alter the absorption of ARQ 197 (e.g., uncontrolled nausea, vomiting,
             diarrhea, malabsorption syndrome, or significant small bowel resection)

          -  Patients with an active bleeding diathesis