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Combining Ipilimumab With Abiraterone Acetate Plus Prednisone in Chemotherapy and Immunotherapy-naïve Patients With Progressive Metastatic Castration-resistant Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01688492
Recruitment Status : Active, not recruiting
First Posted : September 20, 2012
Last Update Posted : September 10, 2021
Bristol-Myers Squibb
Northwestern University
Oregon Health and Science University
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Ipilimumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2012
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: ipilimumab
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.
Drug: Ipilimumab
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.

Primary Outcome Measures :
  1. 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.

  2. 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

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Chemotherapy- and immunotherapy-naïve patients with progressive metastatic CRPC are eligible.

  • Age 18 or older, and be willing and able to provide informed consent.
  • Histologically or cytologically confirmed adenocarcinoma of the prostate at either MSKCC or at the participating site.
  • Castrate serum testosterone level, ≤ 1.73 nmol/L (50 ng/dL), at the Screening visit.
  • Ongoing androgen deprivation therapy with a GnRH analogue or bilateral orchiectomy (ie, surgical or medical castration).
  • Metastatic disease on imaging (e.g., bone scan, CT, MRI). Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible. If lymph node metastasis is the only evidence of metastasis, it must be ≥ 2 cm in diameter.
  • Progressive disease at study entry defined by PSA and/or radiographic criteria according to the PCWG2.
  • Karnofsky performance status of ≥80-100, and estimated life expectancy of ≥ 6 months.
  • Toxicities related to prior therapy must either have returned to ≤ Grade 1 or baseline or been deemed irreversible and in the opinion of the Investigator not worsened.
  • Able to swallow the study drug and comply with study requirements.

Exclusion Criteria:

  • History of another malignancy within the previous 5 years other than nonmelanomatous skin cancer.
  • Absolute neutrophil count < 1,500/μL, or platelet count < 75,000/μL, or hemoglobin < 5.6 mmol/L (9 g/dL) at the Screening visit. (NOTE: patients may not have received any growth factors within 7 days or blood transfusions within 28 days of the hematologic laboratory values obtained at the Screening visit).
  • Serum bilirubin ≥ 1.5 x ULN or for patients with Gilbert's disease, ≥3 mg/dL at the Screening visit; AST or ALT ≥ 2.5 x ULN, (for patients with known liver metastasis, AST or ALT ≤ 5 x ULN is allowed) at the Screening visit.
  • Creatinine > 177 μmol/L (2 mg/dL), albumin < 30 g/L (3.0 g/dL), potassium ≤ 3.5 mEq/L at the Screening visit.
  • Clinically significant cardiovascular disease including myocardial infarction within 6 months, uncontrolled angina within 3 months, congestive heart failure New York Heart Association (NYHA) class 3 or 4, uncontrolled hypertension as indicated by systolic blood pressure > 160 mmHg or diastolic blood pressure > 95 mmHg at the Screening visit.
  • Major surgery or radiation therapy within 4 weeks of enrollment (Day 1 Visit).
  • Treatment with antiandrogens (eg, bicalutamide, flutamide, or nilutamide) within 4 weeks of enrollment (Day 1 visit). Concomitant therapy with any of the agents listed in Section 4.3.2 is prohibited.
  • History of progression of prostate cancer disease while receiving ketoconazole. Prior use or participation in a clinical trial of an investigational agent that blocks androgen synthesis (eg, abiraterone acetate, TAK-700, TAK-683, TAK-448), chemotherapy, or immunological agents (eg, immune modulators, cytokines, vaccines, or antibody-delivered chemotherapy). The use of denosumab for bone metastasis is permitted.
  • Known allergy to any of the compounds under investigation.
  • The patient has uncontrolled or significant medical condition other than cancer, that would prevent the participation in the study or make this protocol unreasonably hazardous, in the opinion of the investigator, including but not limited to:
  • Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (eg, Guillain-Barre syndrome and myasthenia gravis).
  • Known or suspected brain metastasis, or untreated leptomeningeal disease.
  • Active infection or other medical condition that would make prednisone use contraindicated.
  • Active or symptomatic viral hepatitis or chronic liver disease.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01688492

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United States, Illinois
Northwestern University
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
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Bristol-Myers Squibb
Northwestern University
Oregon Health and Science University
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Principal Investigator: Daniel C. Danila, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center Identifier: NCT01688492    
Other Study ID Numbers: 12-120
First Posted: September 20, 2012    Key Record Dates
Last Update Posted: September 10, 2021
Last Verified: September 2021
Keywords provided by Memorial Sloan Kettering Cancer Center:
MDX-010 (Ipilimumab)
castration resistant prostate cancer (CRPC)
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Prostatic Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action