Hormone Therapy and Ipilimumab in Treating Patients With Advanced Prostate Cancer

NCT00170157 | Completed Phase 2 Results

• 3 other identifiers: MC0253NCI-2009-01214P30CA015083
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin, flutamide, or bicalutamide may lessen the amount of androgens made by the body. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving antihormone therapy together with ipilimumab may kill more tumor cells. PURPOSE: This randomized phase II trial is study how well giving hormone therapy and ipilimumab together works in treating patients with advanced prostate cancer.

Conditions

Prostate Adenocarcinoma; Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage III Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants Progression-free at 18 Months

  PSA progression is defined as a rise in PSA to \>4.0 ng/mL demonstrated twice in measurements taken two weeks apart.

  18 months from the start of AA therapy

Secondary Outcomes (1)

• Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response

  3 months

Study Arms (2)

Arm I

EXPERIMENTAL

Patients receive either leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) on days 0, 28, and 56. Patients also receive oral flutamide three times daily or oral bicalutamide once daily. Treatment with antiandrogen (AA) therapy continues for 3 months (3-4 months for patients who initiated AA therapy \<= 21 days prior to enrollment) in the absence of disease progression or unacceptable toxicity. Patients receive ipilimumab IV over 90 minutes on day 7 (within 7-28 days post-initiation of AA therapy for patients who initiated AA therapy \<= 21 days prior to enrollment) of AA therapy.

Drug: Bicalutamide; Drug: Flutamide; Drug: Goserelin Acetate; Drug: Ipilimumab; Drug: Leuprolide Acetate; Other: Pharmacological Study

Arm II

ACTIVE COMPARATOR

Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression.

Drug: Bicalutamide; Drug: Flutamide; Drug: Leuprolide Acetate; Other: Pharmacological Study

Interventions

Bicalutamide DRUG

Given orally

Also known as: Casodex, Cosudex, ICI 176,334, ICI 176334

Arm I; Arm II

Flutamide DRUG

Given orally

Also known as: 4'-Nitro-3'-trifluoromethylisobutyranilide, Apimid, Chimax, Drogenil, Euflex, Eulexin, Eulexine, Flucinom, Flucinome, Flugerel, Fluken, Flulem, FLUT, Fluta-Gry, Flutabene, Flutacan, Flutamex, Flutamin, Flutan, Flutaplex, Fugerel, Grisetin, Niftolid, Oncosal, Profamid, Prostacur, Prostadirex, Prostica, Prostogenat, SCH 13521, Tafenil, Tecnoflut, Testotard

Arm I; Arm II

Goserelin Acetate DRUG

Given SC

Also known as: ZDX, Zoladex

Arm I

Ipilimumab DRUG

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Arm I

Leuprolide Acetate DRUG

Given IM

Also known as: A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur

Arm I; Arm II

Pharmacological Study OTHER

Correlative study

Arm I; Arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• NOTE: All values must be obtained =\< 14 prior to study entry
• An initial PSA \>= 4.0 ng/mL (Hybritech Assay)
• For those patients who have received hormone therapy =\< 21 days, a documented PSA of \>= 4.0 prior to initiation of hormone therapy is acceptable.
• For patients who are post radical prostatectomy, a rising PSA is acceptable.
• Adequate organ function defined as: WBC \>= 3,000/uL; platelets \>= 75,000/uL; total bilirubin =\< 1.5 mg/dL; transaminases =\< 2.5 x upper limit of normal (ULN); serum creatine =\< 2.0 mg/dL or calculated creatinine clearance \>= 60 mL/min
• ECOG performance status of 0-2
• Able to understand and sign informed consent

You may not qualify if:

• Underlying other serious medical condition which, in the opinion of the investigator precludes study participation; this includes immune-suppressive disease such as AIDS or autoimmune disorders such as multiple sclerosis, lupus, or myasthenia gravis
• Patients not recovered from major infections and/or surgical procedures
• Prior hormonal therapy \> 21 days prior to enrollment, including estrogens, LH/RH agonists, or antiandrogens
• Recent (=\< 3 months of informed consent) usage of immune-suppressive medication including steroids, Immuran, Cyclosporin; topical or inhalational steroid use is permissible
• Prior systemic chemotherapy
• Prior radiation therapy to the prostate
• Prior malignancy, unless the patient has been cancer-free for five years or more
• Uncontrolled underlying medical or psychiatric illness, or serious active infections
• Patient unwilling to complete all required follow-up visits
• History of motor neuropathy considered of the autoimmune origin (e.g. Guillian-Barre Syndrome)
• Concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer
• For patients who elect to undergo the baseline transrectal needle biopsy of the prostate, current usage of systemic anticoagulation therapy, i.e. heparin or Coumadin or inability to discontinue aspirin, aspirin-containing products or ibuprofen for seven days prior to the prostate biopsies required for this study
• No other investigational drugs will be allowed during the study
• Other chemotherapy, radiation therapy, immunotherapy, hormonal therapy, or biologic therapy may not be used while the patient is on study

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide; Flutamide; Goserelin; Ipilimumab; CTLA-4 Antigen; Leuprolide; luprolide acetate gel depot

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Eugene D. Kwon
• Organization: Mayo Clinic

kwon.eugene@mayo.edu

Study Officials

• Eugene Kwon

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 15, 2005
• Study Start: June 1, 2004
• Primary Completion: April 1, 2011
• Study Completion: June 1, 2013
• Last Updated: May 15, 2017
• Results First Posted: January 31, 2014

Record last verified: 2017-01

Locations

US (1)