Combining Ipilimumab With Abiraterone Acetate Plus Prednisone in Chemotherapy and Immunotherapy-naïve Patients With Progressive Metastatic Castration-resistant Prostate Cancer
The purpose of this study is to find out what effects, good and/or bad, taking ipilimumab with abiraterone acetate plus prednisone has on the patient and the prostate cancer. Abiraterone acetate plus prednisone are drugs that lower testosterone (testosterone stimulates prostate cancer growth). Abiraterone acetate plus prednisone is a treatment for patients with prostate cancer.
Abiraterone acetate plus prednisone has not been used together with ipilimumab before. This study will test how they work together. Each patient will receive abiraterone acetate, prednisone and ipilimumab.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study Combining Ipilimumab With Abiraterone Acetate Plus Prednisone in Chemotherapy and Immunotherapy-naïve Patients With Progressive Metastatic Castration-resistant Prostate Cancer|
- safety (Phase I) [ Time Frame: 2 years ]AEs will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grading scale, version 4.0.
- progression-free survival (PFS) Phase II [ Time Frame: 8 months ]which is defined as the time from the start of therapy until the criteria for progression are met
- Changes in PSA kinetics [ Time Frame: 2 years ]PSA levels will be assessed every 4 weeks during the Lead in Therapy, every 3 weeks during the Combination Therapy and every 4 weeks during the Maintenance Therapy. Outcomes will be reported both by the percent change in PSA from baseline and Week 21 (or earlier for those who discontinue therapy) and the maximum decline in PSA using a waterfall plot.
- Measurable disease when present [ Time Frame: 2 years ]Measurable disease in viscera (liver or lung) is defined as per PCWG2 modified RECIST 1.1 as a lesion ≥10 mm in its longest diameter as measured with conventional techniques (ie, CT or MRI). For a lymph node to be considered measurable, the minimum diameter must be ≥20 mm in long axis when assessed by CT scan. All other lesions (or sites of disease) will be considered nonmeasurable disease.
- Evaluate changes in radionuclide bone scan [ Time Frame: 2 years ]Radionucleotide bone scan outcome should be recorded as either new lesions or no new lesions. On bone scan, progression of bone metastases is defined as the appearance of 2 or more new bone lesions compared to the baseline scan. In the case of the first Week 8 and Week 16 assessment scans a confirmatory scan performed 6 weeks later needs to shows 2 or more additional new lesions (for a total of at least 4 new lesions seen since baseline) for progression to be documented (the date of progression is always the date of the first scan showing the change).
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
This multi-institution open label study has a Phase 1 and Phase 2 component. The Phase 1 dose escalation stage is to establish the tolerability of ipilimumab to be used in combination with the standard clinical dose of abiraterone acetate plus prednisone in chemotherapy and immunotherapy-naïve patients with progressive metastatic CRPC. Due to the overlapping potential hepatic toxicity between abiraterone and ipilimumab, a Lead in Therapy with abiraterone plus prednisone for 2 cycles will assess for adverse events related to the abiraterone plus prednisone. Patients, who tolerate well the Lead in therapy as defined by Grade 1 or less AEs, will pursue Combination Therapy. Patients with AEs Grade ≥ 2 after Lead in Therapy will be excluded and replaced. The Phase 2 stage will assess efficacy and confirm an acceptable safety profile of the recommended dose.
Abiraterone acetate (JanssenBiotech, Inc/Johnson & Johnson) 1000 mg orally daily plus prednisone 5 mg orally twice daily will be administered continuously during the duration of the trial. Starting at cycle 3 (Combination Therapy), Ipilimumab (Bristol-Myers Squibb) will be infused intravenously (IV) once every 3 weeks for a total of 4 infusions.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01688492
|United States, Illinois|
|Evanston, Illinois, United States, 60208|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Daniel C. Danila, MD||Memorial Sloan Kettering Cancer Center|