Ipilimumab + Androgen Depravation Therapy in Prostate Cancer

NCT ID: NCT01377389

Last Updated: 2023-09-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-17
• Study Completion Date: 2017-04-07

Brief Summary

The goal of this clinical research study is to learn if ipilimumab in combination with either Lupron® (leuprolide), Zoladex® (goserelin), or Firmagon® (degarelix) can affect prostate-specific antigen (PSA) levels in patients with prostate cancer. Researchers also want to learn if these drug combinations affect the body's immune system. The safety of these drug combinations will also be studied.

Detailed Description

The Study Drugs:

Ipilimumab is designed to block the activity of cells that decrease the immune system's ability to fight cancer.

Leuprolide, goserelin, and degarelix are designed to help stop the body from making testosterone (a male sex hormone that prostate cancer cells need to survive), which may slow the growth of cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive either leuprolide, goserelin or degarelix . The drug you receive will depend on what the doctor thinks is in your best interest and/or which drug your insurance provider will help to cover. Leuprolide is given through a needle in the muscle. Goserelin and degarelix are given through a needle under the skin in the abdomen. Beginning at Week 1, you will receive the drug 1 time every month or every 3 months for up to 8 months. Your doctor will tell you more about which dosing schedule you will use.

You will also receive ipilimumab by vein over about 90 minutes at Weeks 5, 9, 13, and 17. Your blood pressure will be measured every 30 minutes during the infusion, as well as an hour after you are finished receiving the drug.

Study Visits:

Before each dose of ipilimumab, and every 4 weeks for 6 months after the last dose of ipilimumab, and every 12 weeks after that, the following tests and procedures will be performed:

• You will have a physical exam.
• You will be asked about any other drugs and/or treatments you may be receiving.
• You will be asked about any side effects you may have experienced.
• Your performance status will be recorded.
• Blood (about 3 teaspoons) will be drawn for routine tests and to measure your protein, PSA, and testosterone levels, and to check the function of your pancreas, thyroid, and adrenal glands.
• Urine will be collected for routine tests.
• This blood will also be tested for other hormone levels to check the function of your thyroid and adrenal glands (before each dose of ipilimumab and 4 weeks after the last dose only).

Every 12 weeks, you will have the same imaging scans that you had at screening.

Length of Study:

You may receive the study drugs for up to 8 months. You will remain on study for as long as the disease remains stable. You will be taken off study treatment if you have intolerable side effects or if the disease gets worse.

End-of-Study Treatment/Observation Visit:

Within 14 days after your disease gets worse, the following tests and procedures will be performed:

• You will have a physical exam.
• You will be asked about any drugs and/or treatments you may be receiving.
• You will be asked about any side effects you may have experienced.
• Blood (about 3 teaspoons) will be drawn for routine tests. This blood will also be tested to measure your protein, PSA, and testosterone levels, and to check the function of your pancreas, thyroid, and adrenal glands.
• You will have the same imaging scans that you had at screening.

Long-Term Follow-Up:

A member of the study staff will check up on you about every 6 months after your End-of-Study Treatment/Observation Visit. This will consist of a phone call, an e-mail, or a review of your medical and/or other records. If you are contacted by phone, the call will only last a few minutes.

This is an investigational study. Leuprolide, goserelin, and degarelix are FDA approved and commercially available for the treatment of prostate cancer. Ipilimumab is FDA approved and commercially available for melanoma. Its use to treat prostate cancer is investigational.

Up to 48 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions

Prostate Cancer

Study Design

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

Study Groups

Ipilimumab + ADT

Ipilimumab 10 mg/kg intravenous (IV) Weeks 5, 9, 13, and 17 plus Androgen Depravation Therapy (ADT) of either Leuprolide 7.5 mg intramuscular (IM) , Goserelin 3.6 mg subcutaneous (SQ) or Degarelix 80 mg SQ once a month for 8 months beginning Week 1.

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: DRUG

10 mg/kg by vein over 90 minutes once every 4 weeks, for 4 weeks.

Leuprolide

Intervention Type: DRUG

7.5 mg intramuscular once a month for 8 months

Goserelin

Intervention Type: DRUG

3.6 mg subcutaneous once a month for 8 months

Degarelix

Intervention Type: DRUG

80 mg subcutaneous once a month for 8 months

Interventions

Ipilimumab

10 mg/kg by vein over 90 minutes once every 4 weeks, for 4 weeks.

Intervention Type: DRUG

Leuprolide

7.5 mg intramuscular once a month for 8 months

Intervention Type: DRUG

Goserelin

3.6 mg subcutaneous once a month for 8 months

Intervention Type: DRUG

Degarelix

80 mg subcutaneous once a month for 8 months

Intervention Type: DRUG

Other Intervention Names

Yervoy; BMS-734016; MDX010; Leuprolide Acetate; Lupron Depot; Zoladex; Firmagon

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed prostate carcinoma.

2. Evidence of metastatic disease on previous bone scan and/or CT scan and/or MRI.

3. Castrate-sensitive disease. Patients already on ADT are eligible as long as the time from initiation of LHRH analog or antagonist is not greater than 1 month AND the total exposure time to the LHRH analog or antagonist will not exceed 8 months (i.e. the effectiveness of current depot LHRH analog or antagonist does not extend beyond 8 months since its initiation).

4. Patients who have received prior hormonal therapy are allowed to participate as long as they have been off hormone ablation for 1.5 times as long as they were on it: e.g. 1) Patients who have received up to 4 months of hormonal ablation are eligible as long as they have been off hormonal ablation for >/= 6 months; 2) Patients who have received 1 year of hormonal ablation are eligible as long as they have been off hormone ablation for >/= 18 months; 3) Patients who have received up to 2 years of hormonal ablation are eligible as long as they have been off hormonal ablation for >/= 3 years have elapsed since its discontinuation.

5. Eastern Cooperative Oncology Group (ECOG) performance status </= 1

6. Patients must have normal organ and marrow function as defined below: a) white blood cell count (WBC) >/= 3000/uL; b) Absolute neutrophil count (ANC) >/= 1500/uL; c) Platelets >/= 100 x 10^3/uL; d) Hemoglobin >/= 9 g/dL; e) Creatinine </= 2mg/dL; f) ALT </= 2.5 x upper limit of normal (ULN) for patients without liver metastases. For patients with liver metastasis ALT </= 5 x ULN is allowed; g) Bilirubin </= 3 x ULN (except for patients with Gilbert's Syndrome, who must have a total bilirubin </= 3mg/dL)

7. Patients included in the study must be >/= 18 years old

8. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

1. Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.

2. Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs: e.g. a condition associated with frequent diarrhea or chronic skin conditions, recent surgery or colonic biopsy from which the patient has not recovered, or partial endocrine organ deficiencies.

3. Patients with known brain metastases.

4. Patients with small cell carcinoma of the prostate.

5. History of other malignancies, other than nonmelanoma skin cancer or Ta or T1 (low grade) bladder carcinomas, unless in complete remission and off therapy for that disease for at least 5 years.

6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, history of congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

7. Known HIV, Hepatitis B, or Hepatitis C.

8. Untreated symptomatic spinal cord compressions.

9. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).

10. Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses).

11. Previous participation in another ipilimumab clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist.

12. History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.

13. Patients who do not agree to practice appropriate birth control methods while on therapy.

14. Concurrent use of 5-alpha reductase inhibitors (finasteride or dutasteride).

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

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ana M. Aparicio, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2011-01125

Identifier Type: REGISTRY

Identifier Source: secondary_id

2009-0378

Identifier Type: -

Identifier Source: org_study_id