Abiraterone Acetate, Prednisone, and Apalutamide With or Without Ipilimumab or Cabazitaxel and Carboplatin in Treating Patients With Metastatic Castration-Resistant Prostate Cancer
A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer
2 other identifiers
interventional
196
1 country
3
Brief Summary
This randomized phase II trial studies the side effects and how well abiraterone acetate, prednisone, and apalutamide work with or without ipilimumab or cabazitaxel and carboplatin in treating patients with castration-resistant prostate cancer that has spread to other places in the body. Androgens can cause the growth of prostate cancer cells. Drugs, such as abiraterone acetate and apalutamide may lessen the amount of androgens made by the body. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as prednisone, cabazitaxel, and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving abiraterone acetate, prednisone, and apalutamide with or without ipilimumab or cabazitaxel and carboplatin may be a better way to treat patients with castration-resistant prostate cancer that has spread to other places in the body.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2016
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 4, 2016
CompletedFirst Posted
Study publicly available on registry
March 9, 2016
CompletedStudy Start
First participant enrolled
May 18, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2028
March 6, 2026
March 1, 2026
11.9 years
March 4, 2016
March 4, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Overall survival (OS)
Will be reported for each arm. Estimated by Bayesian posterior estimates along with the 95% credible intervals and presented using Kaplan-Meier curves.
Up to 4 years
Incidence of adverse events as measured by the method of Thall et al
Will be reported overall as well as by grade and attribution to study drug for each arm.
Up to 4 years
Androgen receptor (AR) response marker signature
Chi-Square tests or chi-square exact tests at a two-sided significance level of 0.05 will be used to evaluate the association between "AR-response marker signatures" (good/bad) and the "allocation serum marker decline" (satisfactory/unsatisfactory).
At baseline
Allocation serum marker decline
Serum levels of prostate specific antigen (PSA) and circulating tumor cells (CTCs) will be evaluated and correlated with AR response marker signatures. Chi-Square tests or chi-square exact tests at a two-sided significance level of 0.05 will be used to evaluate the association between "AR-response marker signatures" (good/bad) and the "allocation serum marker decline" (satisfactory/unsatisfactory). Multivariate logistic regression analysis adjusting for the effects of other baseline factors will also be used to identify factors associated with a satisfactory allocation serum marker profile.
At 8 weeks
Secondary Outcomes (1)
Time to treatment failure (TTF)
Up to 4 years
Study Arms (3)
Arm 2A (abiraterone acetate, prednisone, apalutamide)
EXPERIMENTALPatients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily in the absence of disease progression or unexpected toxicity.
Arm 2B (abiraterone acetate, prednisone, ARN-509, ipilimumab)
EXPERIMENTALPatients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive ipilimumab IV over 90 minutes on day 1 of courses 4-7. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Arm 3(abiraterone, prednisone, ARN509,cabazitaxel,carboplatin)
ACTIVE COMPARATORPatients receive abiraterone acetate PO daily, prednisone PO BID, and apalutamide PO daily. Patients also receive cabazitaxel IV over 60 minutes and carboplatin IV, over 60 minutes on day 1 of courses 4-13. Courses repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
Interventions
Given PO
Given PO
Given IV
Given IV
Given IV
Correlative studies
Given PO
Eligibility Criteria
You may qualify if:
- Each patient must meet the following criteria to be enrolled in this study:
- Willing and able to provide written informed consent.
- Male aged 18 years and above.
- Histologically or cytologically confirmed adenocarcinoma of the prostate.
- Presence of metastatic disease documented on imaging studies (bone scan, CT and/or MRI scans).
- Patients must have documented evidence of progressive disease as defined by any of the following: a) PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least \>/= 1.0 ng/mL; b) New or increasing non-bone disease (RECIST 1.1 criteria); c) Positive bone scan with 2 or more new lesions (PCWG3).
- Surgically or ongoing medically castrated, with baseline testosterone levels of ≤ 50 ng/dL (≤ 2.0 nM).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2.
- Hemoglobin ≥ 7.5 g/dL in the presence of bone marrow involvement independent of transfusion and/or growth factors within 3 months prior to enrollment.
- Platelet count ≥100,000/μL independent of transfusion and/or growth factors within 3 months prior to enrollment.
- Serum albumin ≥3.0g/dL.
- Medications known to lower the seizure threshold (see Appendix H under prohibited medications) must be discontinued or substituted at least 4 weeks prior to study entry.
- Absolute neutrophil count (ANC) ≥ 1,500/mm3
- Calculated creatinine clearance (Cockcroft-Gault Equation) ≥ 40 mL/min.
- Serum potassium ≥ Institutional Lower Limit of Normal (ILLN).
- +5 more criteria
You may not qualify if:
- Patients who meet any of the following criteria will be excluded from the study:
- Prior or Concurrent Treatments:
- Any prior treatment with:
- Ipilimumab
- Treatment within 28 days of Cycle1 Day1:
- Any other systemic therapy for prostate cancer (with the exception of LHRH agonists and LHRH antagonists for testosterone suppression Sipuleucel-T, and bisphosphonates and RANK-ligand inhibitors for bone metastases which are allowed).
- Any other investigational product.
- Any medications listed in Appendix H
- Treatment within 12 months of Cycle 1 Day 1 with any Cyp17-lyase inhibitor, any 2 nd generation AR antagonist (e.g. enzalutamide), cabazitaxel orcarboplatin.
- Patients treated with any Cyp17-lyase inhibitor, any 2nd generation AR antagonist (e.g. enzalutamide), cabazitaxel or carboplatin whose disease progressed while on treatment or within 3 months of its discontinuation. (Patients who have received any of these treatments more than 12 months from study entry and whose disease did not progress while on treatment or within 3 months of its discontinuation are allowed on study).
- Patients whose disease is refractory (defined as evidence of disease progression while on drug or within 3 months of its discontinuation) to more than 2 lines of chemotherapy. Any number of chemotherapies to which the patient's disease is not refractory are allowed, as long as time on treatment did not exceed 6 months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment).
- Flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 and Bicalutamide (Casodex) or nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1 Exceptions: if progression is documented prior to this time interval, or if patient is deemed by the treating physician to be highly unlikely to respond to AR inhibitor withdrawal (e.g. if PSA did not decline for ≥3 months in response to AR inhibitor given as a second line or later intervention, or if patient has symptoms attributable to disease progression) only a 3 day washout prior to Cycle 1, Day 1 will be required for any of them.
- Radiation therapy for treatment of the primary tumor within 6 weeks of Cycle 1, Day 1. Patients who have received palliative radiation and recovered areeligible.
- Any chronic medical condition requiring a higher dose of corticosteroid than 10mg prednisone/prednisolone daily. Use of inhaled, intranasal, intra-articular and topical steroids are acceptable, as is a short course (i.e. ≤ 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans.
- Concurrent illnesses:
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (3)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MD Anderson in Katy
Houston, Texas, 77094, United States
MD Anderson in Sugar Land
Sugar Land, Texas, 77478, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ana Aparicio
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 4, 2016
First Posted
March 9, 2016
Study Start
May 18, 2016
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
March 31, 2028
Last Updated
March 6, 2026
Record last verified: 2026-03