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

This study is currently recruiting participants.
Verified November 2013 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT01498978
First received: December 20, 2011
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

This phase II trial studies show how well ipilimumab works when given together with androgen suppression therapy in treating patients with metastatic hormone-resistant prostate cancer. 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. Androgens 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
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 (=< 0.2ng/ml) [ Time Frame: Every 3 weeks for up to 12 weeks ] [ 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.

  • Fraction of patients who achieve an undetectable PSA (=< 0.2ng/ml) [ Time Frame: Every 6 weeks starting from week 12 through week 24 ] [ 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.

  • Fraction of patients who achieve an undetectable PSA (=< 0.2ng/ml) [ Time Frame: Every 3 months up to 5 years starting after week 24 ] [ 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 [ Time Frame: Every 3 weeks during the first 4 courses, every 6 weeks during weeks 12-24, and then every 3 months through year 5 ] [ Designated as safety issue: No ]
    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. Estimated using the Kaplan-Meier method.

  • Time to progression by any measure [ Time Frame: Weeks 12, 24, and 48 and then every 3 months for up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method. Tumor assessments will be made using modified World Health Organization (WHO) criteria.

  • Time to death from any cause [ Time Frame: Every 3 months for up to 5 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Number of patients with IRAEs [ Time Frame: Every 3 weeks during the first 4 courses of ipilmumab and then every 12 weeks during the second 4 courses of ipilimumab ] [ Designated as safety issue: No ]
    Defined as an AE of unknown etiology associated with drug exposure and consistent with an immune phenomenon. Tabulated for each treatment group and summarized according to major organ categories of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  • Correlation between IRAEs and clinical outcomes [ Time Frame: Every 3 weeks during the first 4 courses, every 12 weeks during the second 4 courses, and then every 3 months through year 5 ] [ Designated as safety issue: No ]
    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: Day 1 of courses 1-4 ] [ 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: Day 1 of courses 1-4 ] [ 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: December 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (monoclonal antibody therapy)
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 four additional doses.
Biological: Ipilimumab
Given IV
Other Name: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, MOAB CTLA-4, monoclonal antibody CTLA-4, Yervoy

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).

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 four additional doses.

After completion of study treatment, patients are followed up every 3 months for up to 5 years.

  Eligibility

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

  • Prior history of pelvic radiation associated with significant radiation proctitis within 12 months prior to planned first infusion of ipilimumab; for the purpose of this protocol, radiation proctitis is defined as diarrhea that reached a level of grade 2 or grade 3, that occurred within one month of radiation treatment, and that was of 7 days duration or longer
  • 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, superficial bladder cancer or carcinoma in situ of the cervix
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01498978

Contacts
Contact: Tim Newby 5034943456 newbyt@ohsu.edu
Contact: Tom Beer 503-494-0365 beert@ohsu.edu

Locations
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Tom Beer, M.D.       Beert@ohsu.edu   
Contact: Tim Newby       newbyt@ohsu.edu   
Principal Investigator: Tomasz Beer, M.D.         
Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Principal Investigator: Tom Beer, MD 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: OHSU-5254, BMS#CA184059, NCI-2011-03556
Study First Received: December 20, 2011
Last Updated: November 18, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgens
Antibodies
Antibodies, Monoclonal
Cytotoxic T-lymphocyte antigen 4
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 16, 2014