Trial record 1 of 1 for:    NCT01576172
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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 March 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: July 22, 2014
Last verified: March 2014

April 11, 2012
July 22, 2014
March 2012
June 2015   (final data collection date for primary outcome measure)
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.
Confirmed PSA response rate [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01576172 on ClinicalTrials.gov Archive Site
  • 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.
  • Rates of PSA decline [ Designated as safety issue: No ]
  • Objective response rates [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Toxicity of abiraterone and abiraterone + ABT-888 described by type, grade, and frequency for each treatment and arm [ Designated as safety issue: Yes ]
  • Changes in CTCs status from baseline to treatment [ Designated as safety issue: No ]
  • Concordance of the ETS fusion status between samples (primary, metastatic, and CTCs) [ Designated as safety issue: No ]
  • PTEN loss as a predictive biomarker of response [ Designated as safety issue: No ]
  • PARP1 activity as a predictive biomarker of response [ Designated as safety issue: No ]
  • SNPs predictive of response [ Designated as safety issue: No ]
  • RNA levels from baseline to treatment [ Designated as safety issue: No ]
  • 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.
Not Provided
 
Abiraterone Acetate and Prednisone With or Without Veliparib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer
A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer

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.

PRIMARY OBJECTIVES:

I. To evaluate the role of v-ets erythroblastosis virus E26 oncogene (ETS) gene fusion as a predictive biomarker for response to hormone therapy (abiraterone [abiraterone acetate]) alone or hormone therapy plus poly adenosine diphosphate-ribose polymerase 1 (PARP-1) targeted therapy (ABT-888 [veliparib]) in patients with metastatic castration resistant prostate cancer.

II. To evaluate whether the addition of PARP-1 targeted therapy is superior to hormone therapy alone based on ETS gene fusion status.

SECONDARY OBJECTIVES:

I. Rate of prostate-specific antigen (PSA) declines. II. Objective response rate. III. Progression-free survival. IV. Evaluate the qualitative and quantitative toxicity of abiraterone acetate with and without ABT-888.

TERTIARY OBJECTIVES:

I. To determine the concordance in fusion status among prostate cancer samples from the primary site, biopsied metastasis, and circulating tumor cells (CTCs).

II. To assess if ETS fusion status in the CTCs, at baseline, 12 weeks, and disease progression (or when off study) is associated with response to therapy.

III. To evaluate if the number of CTCs, as well as the expression levels of androgen receptor, RAD51 recombinase (RAD51), and gamma-H2A histone family, member X (H2aX) foci in the CTCs at baseline, at 12 weeks, and at disease progression in all patients is associated with response to therapy.

IV. To determine the role of phosphatase and tensin homolog (PTEN) loss as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888.

V. To determine the role of PARP1 activity as a predictive biomarker of response to abiraterone, alone or in combination with ABT-888.

VI. To perform next-generation sequencing for discovery of novel gene fusions in prostate cancers negative for ETS fusions.

VII. To perform germline single nucleotide polymorphism (SNP) analysis of genes involved in hormone synthesis, transport, binding, metabolism, and degradation for discovery of novel SNPs predictive of response to abiraterone, alone or in combination with ABT-888.

VIII. To determine if ETS fusion ribonucleic acid (RNA) levels in blood are predictive of response to abiraterone, alone or in combination with ABT-888.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive abiraterone acetate orally (PO) once daily (QD) and prednisone PO twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: 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.

After completion of study treatment, patients are followed up every 6 months for up to 2 years.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Drug: abiraterone acetate
    Given PO
    Other Names:
    • CB7630
    • Zytiga
  • Drug: prednisone
    Given PO
    Other Names:
    • DeCortin
    • Deltra
  • Drug: veliparib
    Given PO
    Other Name: ABT-888
  • Other: laboratory biomarker analysis
    Correlative studies
  • 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.
    Interventions:
    • Drug: abiraterone acetate
    • Drug: prednisone
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: abiraterone acetate
    • Drug: prednisone
    • Drug: veliparib
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
148
Not Provided
June 2015   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
United States
 
NCT01576172
NCI-2012-01149, NCI-2012-01149, CDR0000730114, UCCRC-IL057, 12-0109, 9012, U01CA070095, N01CM00071, N01CM00038, U01CA062491, N01CM00039, P30CA014599
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Maha Hussain University of Chicago
National Cancer Institute (NCI)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP