Ipilimumab + Androgen Deprivation Therapy in Prostate Cancer

Tracking Information
First Submitted Date ICMJE	June 17, 2011
First Posted Date ICMJE	June 21, 2011
Last Update Posted Date	April 12, 2018
Actual Study Start Date ICMJE	June 17, 2011
Actual Primary Completion Date	April 7, 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 17, 2011)	Proportion of Participants achieving a PSA ≤ 0.2ng/mL at Month 7 [ Time Frame: Baseline to 7 months ]; Prostate-specific antigen (PSA) conducted by the Simon's optimal two-stage design (Simon, 1989). Antitumor activity assessed through serial PSA measurements (blood tests) at pre-determined time points.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01377389 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Ipilimumab + Androgen Deprivation Therapy in Prostate Cancer
Official Title ICMJE	A Phase II Study of Ipilimumab PLUS Androgen Deprivation Therapy in Castrate Sensitive Prostate Carcinoma
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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Prostate Cancer
Intervention ICMJE	Drug: Ipilimumab 10 mg/kg by vein over 90 minutes once every 4 weeks, for 4 weeks. Other Names: Yervoy BMS-734016 MDX010; Drug: Leuprolide 7.5 mg intramuscular once a month for 8 months Other Names: Leuprolide Acetate Lupron Depot; Drug: Goserelin 3.6 mg subcutaneous once a month for 8 months Other Name: Zoladex; Drug: Degarelix 80 mg subcutaneous once a month for 8 months Other Name: Firmagon
Study Arms	Experimental: Ipilimumab + ADT; Ipilimumab 10 mg/kg intravenous (IV) Weeks 5, 9, 13, and 17 plus Androgen Deprivation 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.; Interventions: Drug: Ipilimumab; Drug: Leuprolide; Drug: Goserelin; Drug: Degarelix
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 10, 2017)	30
Original Estimated Enrollment ICMJE; (submitted: June 17, 2011)	46
Actual Study Completion Date	April 7, 2017
Actual Primary Completion Date	April 7, 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Histologically or cytologically confirmed prostate carcinoma.; Evidence of metastatic disease on previous bone scan and/or CT scan and/or MRI.; 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).; 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.; Eastern Cooperative Oncology Group (ECOG) performance status </= 1; 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); Patients included in the study must be >/= 18 years old; Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: 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.; 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.; Patients with known brain metastases.; Patients with small cell carcinoma of the prostate.; 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.; 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.; Known HIV, Hepatitis B, or Hepatitis C.; Untreated symptomatic spinal cord compressions.; Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab).; 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).; Previous participation in another ipilimumab clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist.; History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.; Patients who do not agree to practice appropriate birth control methods while on therapy.; Concurrent use of 5-alpha reductase inhibitors (finasteride or dutasteride).
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01377389
Other Study ID Numbers ICMJE	2009-0378; NCI-2011-01125 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Not Provided
Responsible Party	M.D. Anderson Cancer Center
Study Sponsor ICMJE	M.D. Anderson Cancer Center
Collaborators ICMJE	Bristol-Myers Squibb
Investigators ICMJE	Principal Investigator: Ana M. Aparicio, MD M.D. Anderson Cancer Center
PRS Account	M.D. Anderson Cancer Center
Verification Date	April 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP