Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
Condition: Castration-Resistant Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer AJCC v7
MeSH terms: Carcinoma; Prostatic Neoplasms
Intervention: Abiraterone Acetate; Laboratory Biomarker Analysis; Prednisone; Veliparib
Intervention description: Given PO; Correlative studies; Given PO; Given PO
Intervention MeSH terms: Prednisone; Cortisone; Abiraterone Acetate; Veliparib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 159.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies abiraterone acetate and prednisone together with
      veliparib to see how well it works compared to abiraterone acetate and prednisone alone in
      treating patients with castration-resistant prostate cancer that has spread from the primary
      site to other places in the body. Androgens can cause the growth of prostate cancer cells.
      Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by
      the body. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed
      for cell growth. Giving abiraterone acetate together with prednisone and veliparib may work
      better than abiraterone acetate and prednisone alone in treating patients with
      castration-resistant prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a histologic or cytologic diagnosis of prostate cancer

          -  Have progressive metastatic castration-resistant prostate cancer, on
             androgen-deprivation therapy, based on at least one of the following criteria:

               -  PSA progression defined as 25% increase over baseline value with an increase in
                  the absolute value of at least 2 ng/mL that is confirmed by another PSA level
                  with a minimum of a 1-week interval with a minimum PSA of 2 ng/mL

               -  Progression of bidimensionally measurable soft tissue (nodal metastasis) assessed
                  within one month prior to registration by a computed tomography (CT) scan or
                  magnetic resonance imaging (MRI) of the abdomen and pelvis

               -  Progression of bone disease (evaluable disease) (new bone lesion[s]) by bone scan

          -  Agree to undergo a biopsy of at least 1 metastatic site for gene-fusion status
             analysis; adequate archival metastatic tissue can be used if available in lieu of a
             biopsy; patients will only be eligible for protocol therapy if the biopsy has tumor
             and the tissue is evaluable for ETS fusion status

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Have testosterone < 50 ng/dL; patients must continue primary androgen-deprivation with
             a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone
             orchiectomy

          -  Patients must discontinue antiandrogen therapy for at least 4 weeks (e.g. flutamide,
             bicalutamide, nilutamide) prior to registration with no evidence of a falling PSA
             after washout; patients on steroids are eligible as long as they will be switched to
             prednisone

          -  Have no prior exposure to cytochrome 450 family 17(CYP-17) (other than ketoconazole)
             or PARP inhibitors for prostate cancer; patients with prior exposure to ketoconazole
             are eligible

          -  Patients with up to 2 prior chemotherapy regimens are eligible

          -  Obtained within 14 days prior to registration: White blood cells (WBC) >= 3,000/ul

          -  Obtained within 14 days prior to registration: Absolute neutrophil count (ANC) >=
             1,500/ul

          -  Obtained within 14 days prior to registration: Platelet count >= 100,000/ul

          -  Obtained within 14 days prior to registration: Serum creatinine =< 1.5 x the
             institutional upper limits of normal or corrected creatinine clearance of >= 50
             mg/ml/hr/1.73 m^2 body surface area (BSA)

          -  Obtained within 14 days prior to registration: Potassium >= 3.5 mmol/L

          -  Obtained within 14 days prior to registration: Bilirubin within the institutional
             limits of normal

          -  Obtained within 14 days prior to registration: Serum glutamic oxaloacetic transaminase
             (SGOT) (aspartate aminotransferase [AST]) =< 2 times upper limit of normal

          -  Obtained within 14 days prior to registration: Serum glutamate pyruvate transaminase
             (SGPT) (alanine aminotransferase [ALT]) =< 2 times upper limit of normal

          -  Measured within 28 days prior to administration of ABT-888: >= 10.0 g/dL hemoglobin
             (Hb) with no blood transfusion in the past 28 days

          -  Men must agree to use effective contraception during treatment and for at least 1 week
             after the last administration of therapy

          -  Patients must be able to take oral medication without crushing, dissolving, or chewing
             tablets

          -  Patients may have received prior radiation therapy or surgery; however, at least 21
             days must have elapsed since completion of radiation therapy or surgery and patient
             must have recovered from all side effects at the time of registration

          -  Ability to understand and the willingness to sign a written informed-consent document
             that is approved by the local institutional review board

        Exclusion Criteria:

          -  Patients may not be receiving any other investigational agents; any prior
             investigational products must be stopped at least 14 days (2-week washout) prior to
             registration

          -  Patients who have had chemotherapy, radiotherapy or oral antifungal agents
             (ketoconazole, itraconazole, fluconazole) within 3 weeks prior to entering the study
             or those who have not recovered (e.g. back to baseline or grade 1) from adverse events
             due to agents administered more than 3 weeks earlier

               -  There is a potential drug interaction when abiraterone is concomitantly used with
                  a cytochrome P450 family 2, subfamily D, polypeptide 6 (CYP2D6) substrate narrow
                  therapeutic index (e.g., thioridazine, dextromethorphan), or strong cytochrome
                  P450 family 3, subfamily A, polypeptide 4 [CYP3A4] inhibitors (e.g., atazanavir,
                  erythromycin, indinavir, itraconazole, Ketoconazole, nefazodone, nelfinavir,
                  ritonavir, saquinavir, telithromycin, and voriconazole) or strong inducers (e.g.,
                  carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine);
                  caution should be used when patients are on one of these drugs

          -  Patients with history of active seizures are not eligible

          -  Patients with a history of pituitary or adrenal dysfunction, active or symptomatic
             viral hepatitis, or chronic liver disease are not eligible

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ABT-888 or abiraterone

          -  Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other
             herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St John's wort,
             etc.) must be discontinued before registration; patients must not be planning to
             receive any concurrent cytotoxic chemotherapy, surgery, or radiation therapy during
             protocol treatment; hormonal-acting agents (including diethylstilbestrol/DES,
             aldosterone, and spironolactone) are forbidden during the trial and must be stopped
             prior to registration; no washout period will be required for any of these agents;
             patients on megestrol acetate for hot flashes are allowed to continue therapy

          -  Patients on stable doses of bisphosphonates or denosumab which have been started prior
             to registration may continue on this medication, patients who are not on
             bisphosphonates or denosumab are eligible as long as they initiate therapy prior to
             registration

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure (New York Heart Association class III
             and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements or
             concurrent medications that alter cardiac conduction

          -  Patients with a "currently active" second malignancy other than non-melanoma skin
             cancers are not eligible; patients are not considered to have a "currently active"
             malignancy if they have completed all therapy and are now considered without evidence
             of disease for 1 year

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patients with treatment-related acute myeloid leukemia (AML) (t-AML)/myelodysplastic
             syndrome (MDS) or with features suggestive of AML/MDS. Prior allogeneic bone marrow
             transplant or double umbilical cord blood transplantation