Ipilimumab in Combination With Androgen Suppression Therapy in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
First received: December 20, 2011
Last updated: March 17, 2015
Last verified: March 2015
This phase II trial studies how well ipilimumab works when given together with androgen suppression therapy in treating patients with hormone-resistant prostate cancer that has spread to other parts of the body. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Androgen can cause the growth of prostate cancer. Androgen deprivation therapy may stop the adrenal glands from making androgen. Giving ipilimumab together with androgen suppression therapy may kill more tumor cells.

Condition Intervention Phase
Adenocarcinoma of the Prostate
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Biological: ipilimumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of CTLA Blockade by Ipilimumab Plus Androgen Suppression Therapy in Patients With an Incomplete Response to AST Alone for Metastatic Prostate Cancer

Resource links provided by NLM:

Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Fraction of patients who achieve an undetectable PSA (=< 0.2 ng/ml) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Provided with the exact 95% confidence interval. PSA response as recommended by the Prostate Cancer Clinical Trials Working Group (PCWG2) definitions.

Secondary Outcome Measures:
  • Time to PSA progression, defined as a PSA increase of >= 25% and at least 2 ng/mL from baseline or nadir PSA achieved, confirmed by a second measurement at least three weeks later [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Time to progression by any measure [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Time to death from any cause [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Number of patients with IRAEs, defined as an AE of unknown etiology associated with drug exposure and consistent with an immune phenomenon [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    Tabulated for each treatment group and summarized according to major organ categories of the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes.

  • Clinical outcomes [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The correlation between IRAEs and clinical outcomes will be evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes.

  • Ratio of T regulatory cells to T effector cells [ Time Frame: Up to day 1 of course 4 ] [ Designated as safety issue: No ]
    Evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes.

  • Immune response [ Time Frame: Up to day 1 of course 4 ] [ Designated as safety issue: No ]
    Evaluated using logistic regression for binary endpoints and Cox regression for the time to event outcomes.

Estimated Enrollment: 30
Study Start Date: February 2012
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (ipilimumab)
Patients receive ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses.
Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


I. Proportion of patients who achieve an undetectable prostate-specific antigen (PSA) (=< 0.2 ng/ml) after initiation of ipilimumab therapy.


I. Time to PSA progression. II. Time to progression by any measure. III. Maximum percentage of PSA reduction in each patient. IV. Number of patients with immune related adverse events (IRAEs) and correlation of these with complete PSA response, time to progression, and T cell measurements.

V. Measures of T cell response to therapy with flow cytometry. VI. Response in measurable disease by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

VII. Time to death from any cause. VIII. To examine correlative biomarkers and their relationship to clinical outcomes. Potential biomarkers include, but are not limited to C-reactive protein (CRP), insulin-like growth factor (IGF)-1 and -2, or follicle stimulating hormone (FSH).

XV. Bank samples for future molecular correlative studies, biomarker, or other studies.


Patients receive ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression then receive maintenance ipilimumab IV once every 3 months for 4 additional doses.

After completion of study treatment, patients are followed up every 6 months for up to 5 years.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Willing and able to give written informed consent
  • Histologic diagnosis of adenocarcinoma of the prostate
  • A PSA of > 0.2 ng/ml after 6-18 months of androgen suppression therapy, which may consist of luteinizing hormone-releasing hormone (LHRH) agonist or antagonist alone or the combination of an LHRH agonist or antagonist plus an antiandrogen, such as bicalutamide; androgen suppression therapy will continue without interruption
  • Radiographic evidence of regional or distant metastasis at the time of study enrollment or at the time of diagnosis
  • White blood cell (WBC) >= 2000/uL
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets >= 50 x 10^3/uL
  • Hemoglobin >= 8 g/dL
  • Creatinine =< 3.0 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN for patients without liver metastasis
  • Bilirubin =< 3.0 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • No known active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; patients should be assessed for high risk behaviors that may result in these infections, such as intravenous drug use or multiple sexual partners; the assessment should be noted
  • Eastern Cooperative Oncology Group (ECOG) =< 1
  • Patients receiving any herbal product known to decrease PSA levels (i.e. saw palmetto and prostate cancer [PC]-SPES), or any immunosuppressive dose of systemic or absorbable topical corticosteroid (except prednisone up to 10 mg orally per [q] day, or its equivalent), must discontinue the agent for at least 2 weeks prior to screening; progressive disease must be documented after discontinuation of these products
  • Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to the first infusion with ipilimumab
  • Total testosterone < 50 ng/ml, except in patients with prior orchiectomy, where testosterone does not need to be measured; patients must continue their LHRH agonist therapy throughout study duration
  • Life expectancy >= 6 months; this must be documented
  • Patients who are sexually active with a partner who could become pregnant are to use an effective form of barrier contraception, such as condoms or a partner using oral contraceptive pills; persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped
  • If a patient enters the trial on androgen suppression therapy (AST) that consists of both an LHRH agonist and an oral antiandrogen, both agents should be continued throughout the study; if an antiandrogen is stopped prior to study entry, it should be stopped 4 weeks before for nilutamide and flutamide and 6 weeks before for bicalutamide to ensure that a withdrawal phenomenon does not interfere with interpretation of efficacy results

Exclusion Criteria:

  • Radiation to any area of the body < 28 days prior to randomization
  • Any other active malignancy with the exception of adequately treated basal or squamous cell skin cancer or superficial bladder cancer
  • Autoimmune disease: patients with a history of inflammatory bowel 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 (e.g. myasthenia gravis, Guillain-Barre syndrome); those with immune-mediated skin toxicity (i.e. toxic epidermal necrolysis, Stevens-Johnson syndrome) will also be excluded
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
  • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
  • A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
  • Concomitant therapy with any of the following: interleukin (IL)-2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents (over the counter [OTC]/herbal/prescribed); immunostimulant agents, other than the study agent; other investigational therapies; or chronic use of systemic corticosteroids (greater than prednisone 10 mg orally per day, or its equivalent)
  • Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e., infectious) illness
  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: NCT01498978

United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Mark N. Stein    732-235-5773    einmn@umdnj.edu   
Principal Investigator: Mark N. Stein         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Julie N. Graff    503-220-8262 ext 55688    graffj@ohsu.edu   
Principal Investigator: Julie N. Graff         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Julie Graff OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT01498978     History of Changes
Other Study ID Numbers: 5254, NCI-2011-03556, CA184059, 08-004, 5254, P30CA069533
Study First Received: December 20, 2011
Last Updated: March 17, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 24, 2015