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

NCT ID: NCT01498978

Last Updated: 2020-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-06
• Study Completion Date: 2019-01-19

Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

Conditions

Adenocarcinoma of the Prostate; Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

ipilimumab

Intervention Type: BIOLOGICAL

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

ipilimumab

Given IV

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody; MDX-010; MDX-CTLA-4; monoclonal antibody CTLA-4

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Julie Graff

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Julie Graff

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

OHSU Knight Cancer Institute

Portland, Oregon, United States

Countries

United States

References

Graff JN, Stein MN, Surana R, Al Rabadi L, Liu E, Fong L, Bailey S, Latour E, Newby TA, Moran AE, Beer TM. Phase II Study of Ipilimumab in Men With Metastatic Prostate Cancer With an Incomplete Response to Androgen Deprivation Therapy. Front Oncol. 2020 Aug 7;10:1381. doi: 10.3389/fonc.2020.01381. eCollection 2020.

Reference Type: DERIVED

PMID: 32850444 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2011-03556

Identifier Type: REGISTRY

Identifier Source: secondary_id

CA184059

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

08-004

Identifier Type: OTHER

Identifier Source: secondary_id

5254

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00005254

Identifier Type: -

Identifier Source: org_study_id