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Trial record 1 of 1 for:    Abiraterone and ABT-888 in prostate
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Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01576172
First received: April 11, 2012
Last updated: November 21, 2014
Last verified: September 2014
  Purpose

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 metastatic hormone-resistant prostate cancer. 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. It is not yet known whether giving abiraterone acetate together with prednisone and veliparib is more effective than abiraterone acetate and prednisone alone in treating prostate cancer.


Condition Intervention Phase
Hormone-Resistant Prostate Cancer
Recurrent Prostate Carcinoma
Stage IV Prostate Cancer
Drug: Abiraterone Acetate
Drug: Prednisone
Drug: Veliparib
Other: Laboratory Biomarker Analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Confirmed PSA response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The corresponding binomial confidence intervals will be reported for each arm. A logistic model including treatment group, fusion status, and prior ketoconazole use will be used to determine the interaction between the rates of PSA response between abiraterone and abiraterone + ABT-888 and ETS fusion status.


Secondary Outcome Measures:
  • Rates of PSA decline [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be exhibited using waterfall plots of 12 week PSA decline and maximum PSA decline by treatment arm. Additionally, the rate of PSA decline will be explored using a repeated measures mixed model with the natural log of PSA as the outcome.

  • Objective response rates [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be reported by treatment with corresponding binomial confidence intervals.

  • Progression-free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years ] [ Designated as safety issue: No ]
    Kaplan-Meier methods will be used to describe progression free survival by arm.

  • Grade 4 or greater toxicity of abiraterone acetate and abiraterone acetate + veliparib graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    Will be described by type, grade, and frequency for each treatment and arm.


Other Outcome Measures:
  • CTC enumeration [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    CTCs at baseline will be described by treatment arm and strata.

  • ETS fusion status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Concordance of the ETS fusion status between samples (primary, metastatic, and CTCs) from each patient will be described and tested between the three populations using a generalized kappa. The three pairwise comparisons will also be investigated and McNemar's test and kappa statistic for each will be reported.

  • PTEN expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Logistic models with response as the outcome and loss of PTEN in the specimen will be used to determine if PTEN loss predict response to Abiraterone +/- ABT-888.

  • PARP activity [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Logistic models with response as the outcome and expression levels of PAR in the specimen will be used to determine if PARP activity predict response to Abiraterone +/- ABT-888.

  • SNP identification [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Standard quality control statistical analyses (i.e. Hardy-Weinberg Equilibrium testing) will be performed to analyze SNP assay results. Univariable analyses will be performed to identify candidate SNPs associated with favorable abiraterone outcomes.

  • Change in ERG mRNA levels [ Time Frame: Baseline to up to 2 years ] [ Designated as safety issue: No ]
    Logistic and Cox regression models may be used to explore baseline RNA levels or early changes in RNA levels to predict response and PFS respectively.


Estimated Enrollment: 148
Study Start Date: March 2012
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (abiraterone acetate and prednisone)
Patients receive abiraterone acetate PO QD and prednisone PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga
Drug: Prednisone
Given PO
Other: Laboratory Biomarker Analysis
Correlative studies
Experimental: Arm II (abiraterone acetate, prednisone, and veliparib)
Patients receive veliparib PO BID on days 1-28. Patients also receive abiraterone acetate PO QD and prednisone PO BID on day 1 (day 8 of course 1). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Abiraterone Acetate
Given PO
Other Names:
  • CB7630
  • Zytiga
Drug: Prednisone
Given PO
Drug: Veliparib
Given PO
Other Name: ABT-888
Other: Laboratory Biomarker Analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  • White blood cells (WBC) >= 3,000/uL
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelet count >= 100,000/uL
  • 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)
  • Potassium >= 3.5 mmol/L
  • Bilirubin within the institutional limits of normal
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 2 times upper limit of normal
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 2 times upper limit of normal
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01576172

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Przemyslaw W. Twardowski    626-256-4673ext68218    ptwardowski@coh.org   
Principal Investigator: Przemyslaw W. Twardowski         
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Przemyslaw W. Twardowski    626-256-4673    ptwardowski@coh.org   
Principal Investigator: Przemyslaw W. Twardowski         
University of Southern California/Norris Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: David I. Quinn    323-865-3956    diquinn@usc.edu   
Principal Investigator: David I. Quinn         
City of Hope Medical Group Inc Recruiting
Pasadena, California, United States, 91105
Contact: Stephen C. Koehler    626-396-2900    skhoehler@cohmg.com   
Principal Investigator: Stephen C. Koehler         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Walter M. Stadler    773-702-4150    wstadler@medicine.bsd.uchicago.edu   
Principal Investigator: Walter M. Stadler         
NorthShore University HealthSystem-Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201
Contact: Daniel H. Shevrin    847-570-2515    DShevrin@northshore.org   
Principal Investigator: Daniel H. Shevrin         
United States, Indiana
Indiana University Medical Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Costantine Albany    317-948-8310    calbany@iupui.edu   
Principal Investigator: Costantine Albany         
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21231
Contact: Emmanuel S. Antonarakis    410-502-7528    eantona1@jhmi.edu   
Principal Investigator: Emmanuel S. Antonarakis         
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21287
Contact: Emmanuel S. Antonarakis    410-502-7528    eantona1@jhmi.edu   
Principal Investigator: Emmanuel S. Antonarakis         
United States, Michigan
University of Michigan University Hospital Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Maha H. Hussain    734-936-8906    mahahuss@umich.edu   
Principal Investigator: Maha H. Hussain         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Mark N. Stein    732-235-3336    steinmn@umdnj.edu   
Principal Investigator: Mark N. Stein         
UMDNJ - Robert Wood Johnson University Hospital Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Mark N. Stein    732-235-3336    steinmn@umdnj.edu   
Principal Investigator: Mark N. Stein         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Young E. Whang    919-843-9983    ywhang@med.unc.edu   
Principal Investigator: Young E. Whang         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Paul G. Corn    713-792-2830    pcorn@mdanderson.org   
Principal Investigator: Paul G. Corn         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Contact: Robert B. Montgomery    206-598-0860    rbmontgo@u.washington.edu   
Principal Investigator: Robert B. Montgomery         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Glenn Liu    608-265-8689    gxl@medicine.wisc.edu   
Principal Investigator: Glenn Liu         
Sponsors and Collaborators
Investigators
Principal Investigator: Maha Hussain University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01576172     History of Changes
Other Study ID Numbers: NCI-2012-01149, NCI-2012-01149, CDR0000730114, UCCRC-IL057, 12-0109, 9012, N01CM00038, U01CA062491, P30CA014599, N01CM00039, N01CM00071, U01CA070095
Study First Received: April 11, 2012
Last Updated: November 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Prostatic Diseases
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Prednisone
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014