Neoadjuvant Ipilimumab in Prostate Cancer

Tracking Information
First Submitted Date ICMJE	September 1, 2010
First Posted Date ICMJE	September 2, 2010
Last Update Posted Date	August 22, 2016
Study Start Date ICMJE	September 2010
Actual Primary Completion Date	October 2015 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 1, 2010)	Longitudinal Peripheral Blood Values [ Time Frame: Weekly for 8 weeks ]; Five immunological variables measured on peripheral blood (pb) samples and tumor tissue samples: (i) effector to regulatory T cell ratio (measured in blood and tumor), (ii) CD4+ICOS+ T cells (measured in blood and tumor), (iii) CD8+ICOS+ T cells (measured in blood and tumor), (iv) NY-ESO-1 antibodies (measured only in blood, not tumor), and (v) absolute lymphocyte count (measured only in blood, not tumor). Measurements based on pb samples weeks 0, 1, 4, 7, and measurements from tumor tissue at week 8.
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01194271 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	Neoadjuvant Ipilimumab in Prostate Cancer
Official Title ICMJE	A Neoadjuvant Phase IIa Study of Ipilimumab {Formerly Known as MDX-010 (BMS-734016)} Plus Hormone Ablation in Men With Prostate Cancer Followed by Radical Prostatectomy.
Brief Summary	The goal of this clinical research study is to learn how ipilimumab in combination with Lupron (leuprolide acetate) affects the body's own defense (immune) system before having surgery to remove prostate cancer. The safety of the drug combination will also be studied.
Detailed Description	The Study Drugs: Ipilimumab is designed to cause an immune response in your body by blocking 2 specific molecules that usually block an immune response. This may help to kill cancer cells. Leuprolide acetate is designed to lower the level of testosterone (a male hormone) in the blood. This 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 a leuprolide acetate injection in your muscle. This is considered Week 0. One week later, you will begin treatment with ipilimumab. Ipilimumab will be given by vein over 90 minutes during Weeks 1 and 4 (about 21 days apart). During the infusion, your blood pressure will be measured every 30 minutes, and again an hour after you are finished receiving the drug. Study Visits: At Weeks 0, 1, 4 and 7, the following tests and procedures will be performed: You will have a physical exam, including measurement of your vital signs and weight.; You will be asked about any drugs 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 7-10 tablespoons) will be drawn for routine tests. This blood will also be tested to measure your protein, PSA and testosterone levels, to check the function of your thyroid and adrenal glands, and to test for an immune response. Surgery: About 4 weeks after your second treatment with ipilimumab, you will have surgery to remove your prostate gland. You will be asked to sign a separate consent form that describes the surgery and its risks. A sample of the leftover prostate gland tissue from surgery will be tested for an immune response. On that day, the following tests and procedures will be performed: Between 14 and 24 weeks after your surgery, you will return to the clinic for your post-operative follow-up visit. The following tests and procedures will be performed: You will have a physical exam, including measurement of your vital signs and weight.; Your performance status will be recorded.; You will be asked about any drugs or treatments you may be receiving.; You will be asked about any side effects you have experienced since your last visit.; Blood (about 7-10 tablespoons) will be drawn for routine tests. This blood will also be used to measure your protein, testosterone and PSA levels, to check the function of your thyroid and adrenal glands, and to test for an immune response.; You will have a bone scan, and either a CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease. Length of Study: You will only receive 2 treatments with ipilimumab on this study. You will be on study until 24 weeks after surgery. You will be taken off study if intolerable side effects occur, if the disease gets worse, or if the study doctor thinks it is in your best interest to be taken off study. This is an investigational study. Ipilimumab is not FDA approved or commercially available. Ipilimumab is currently being used for research purposes only. Leuprolide acetate is FDA approved for management of metastatic prostate cancer but is not approved for use before definitive surgery. It is commercially available to treat prostate cancer. Up to 20 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: Leuprolide Acetate 22.5 mg administered as a single intramuscular 3 month depot. Other Name: Lupron Depot; Drug: Ipilimumab 10 mg/kg by vein administered as 2 single doses, 3 weeks apart after hormone therapy. Other Names: BMS-734016 MDX010; Procedure: Radical Prostatectomy Surgery to remove prostate gland approximately 4 weeks after the second dose of Ipilimumab.
Study Arms	Experimental: Neoadjuvant Ipilimumab; Leuprolide Acetate 22.5 mg administered as a single intramuscular 3 month depot + Ipilimumab 10 mg/kg by vein administered as 2 single doses, 3 weeks apart after hormone therapy + Radical Prostatectomy Surgery to remove prostate gland approximately 4 weeks after the second dose of Ipilimumab.; Interventions: Drug: Leuprolide Acetate; Drug: Ipilimumab; Procedure: Radical Prostatectomy
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: October 13, 2015)	19
Original Estimated Enrollment ICMJE; (submitted: September 1, 2010)	20
Actual Study Completion Date	October 2015
Actual Primary Completion Date	October 2015 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Willing and able to give written informed consent;; Histologic Documentation: Histologic documentation of prostatic adenocarcinoma. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible. All eligible patients must have a known Gleason sum based on biopsy or TURP at the time of registration.; Locally Resectable Disease: Patients must have disease (localized or locally advanced) which is deemed by the surgeon to be resectable. Lymph node metastasis or lymph nodes suspicious of harboring metastasis should be deemed surgically resectable by the surgeon.; Determination of high-risk status: Patients must have either: 1) a Prostate biopsy Gleason sum >/= 8 OR 2) PSA >/= 20.; Prior Treatment: No prior treatment for prostate cancer including prior surgery (excluding TURP), pelvic lymph node dissection, radiation therapy, or chemotherapy. Patients who have initiated leuprolide acetate within 1 week of signing consent will be eligible.; Patients must be appropriate candidates for radical prostatectomy. Evidence of underlying cardiac disease should be evaluated prior to enrollment to ensure that patients are not at high risk of cardiac complications.; ECOG performance status of 0 or 1;; Required values for initial laboratory tests: a) WBC >/= 3000/uL; b) ANC >/= 1500/uL, c) Platelets >/= 100 x 10^3/uL; d) Hemoglobin >/= 9 g/dL; e) Creatinine </= 2.0 x ULN; f) AST </= 2.5 x ULN; g) Bilirubin 0 - 1.0 mg/dL, except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/mL;; Men >/= 18 years of age; Patients must agree to practice barrier birth control methods while on therapy, prior to surgery. Exclusion Criteria: Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer.; Autoimmune disease: Patients with a history of Inflammatory Bowel Disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]).; Known HIV or chronic hepatitis.; Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.; Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation, should be excluded from the study.; 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 treatment with other investigational products within 30 days;; Previous enrollment in another MDX-010 (BMS-734016) clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist; Concurrent use of 5-alpha-reductase inhibitors (finasteride, dutasteride).; Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled in this study.
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	NCT01194271
Other Study ID Numbers ICMJE	2009-0135; NCI-2010-01974 ( Registry Identifier: NCI CTRP )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
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: Padmanee Sharma, MD, PHD M.D. Anderson Cancer Center
PRS Account	M.D. Anderson Cancer Center
Verification Date	August 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP