Study of Immunotherapy to Treat Advanced Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

A Randomized, Double-Blind, Phase 3 Trial Comparing Ipilimumab vs. Placebo Following Radiotherapy in Subjects With Castration Resistant Prostate Cancer That Have Received Prior Treatment With Docetaxel

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00861614
• Other study ID #: CA184-043
• Secondary ID: 2008-003314-97
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2009
• Last updated: March 16, 2016
• Start date: May 2009
• Est. completion date: August 2015

Study information

• Verified date: March 2016
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine if advanced prostate cancer patient s that are treated with radiotherapy (RT) plus ipilimumab live longer that those treated with RT alone

Recruitment information / eligibility

• Status: Completed
• Enrollment: 988
• Est. completion date: August 2015
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

• Advanced prostate cancer

• At least 1 bone metastasis

• Testosterone < 50 ng/dl

• Prior treatment with docetaxel

Exclusion Criteria:

• Brain metastasis

• Autoimmune disease

• Known HIV, Hep B, or Hep C infection

• More than 2 prior systemic anticancer regimens for prostate cancer

• Prior treatment on BMS CA180227 for prostate cancer

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Ipilimumab
5 mg/ml solution, Intravenous, 10 mg/kg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase, Up to 24 weeks in Induction, 48+ weeks in the Maintenance Phase, or until Treatment Stopping Criteria are met, withdrawal of consent, lost to follow-up, death, study closure
• Placebo
Solution, Intravenous, 0 mg, Every 3 weeks for up to 4 doses in the Induction Phase. Every 12 weeks in the Maintenance Phase, up to 24 weeks in Induction, 48+ weeks in the Maintenance Phase, or until Treatment Stopping Criteria are met, withdrawal of consent, lost to follow-up, death, study closure

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Caba	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Cordoba
Argentina	Local Institution	La Rioja
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	Rosario	Santa Fe
Argentina	Local Institution	San Miguel De Tucuman	Tucuman
Argentina	Local Institution	San Miguel De Tucuman	Tucuman
Australia	Local Institution	Box Hill	Victoria
Australia	Local Institution	Frankston	Victoria
Australia	Local Institution	Heidelberg	Victoria
Australia	Local Institution	Subiaco	Western Australia
Austria	Local Institution	Salzburg
Austria	Local Institution	Wien
Belgium	Local Institution	Brussels
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Roeselare
Brazil	Local Institution	Curitiba	Parana
Brazil	Local Institution	Curitiba	Sao Paulo
Brazil	Local Institution	Divinopolis	Sao Paulo
Brazil	Local Institution	Fortaleza	Ceara
Brazil	Local Institution	Ijui	Rio Grande Do Sul
Brazil	Local Institution	Mogi Das Cruzes	Sao Paulo
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Sao Paulo
Brazil	Local Institution	Sao Paulo
Canada	Local Institution	Greenfield Park	Quebec
Canada	Local Institution	Montreal	Quebec
Chile	Local Institution	Santiago	Metropolitana
Chile	Local Institution	Santiago - Independencia	Metropolitana
Chile	Local Institution	Santiago De Chile	Metropolitana
Chile	Local Institution	Temuco	Araucania
Chile	Local Institution	Vi?a Del Mar	Valparaiso
Colombia	Local Institution	Bogota
Colombia	Local Institution	Monteria	Cordoba
Czech Republic	Local Institution	Brno
Czech Republic	Local Institution	Hradec Kralove
Czech Republic	Local Institution	Liberec
Denmark	Local Institution	Aalborg
Denmark	Local Institution	Aarhus
Denmark	Local Institution	Herlev
Denmark	Local Institution	Kobenhavn O
Denmark	Local Institution	Odense C
France	Local Institution	Besancon Cedex
France	Local Institution	Bordeaux
France	Local Institution	Clermont-ferrand
France	Local Institution	Marseille Cedex 20
France	Local Institution	Pointe A Pitre
France	Local Institution	Villejuif Cedex
Germany	Local Institution	Berlin
Germany	Local Institution	Bonn
Germany	Local Institution	Eschweiler
Germany	Local Institution	Mannheim
Germany	Local Institution	Wuppertal
Greece	Local Institution	Athens
Hungary	Local Institution	Budapest
Hungary	Local Institution	Gyula
Hungary	Local Institution	Kaposvar
Hungary	Local Institution	Kecskemet
Ireland	Local Institution	Dublin
Ireland	Local Institution	Dublin 7	Dublin
Ireland	Local Institution	Tallaght	Dublin
Israel	Local Institution	Beer Jacob
Israel	Local Institution	Beer-sheva
Israel	Local Institution	Haifa
Israel	Local Institution	Tel Aviv
Israel	Local Institution	Tel Hashomer
Italy	Local Institution	Meldola (fc)
Italy	Local Institution	Milano
Italy	Local Institution	Napoli
Italy	Local Institution	Rimini
Italy	Local Institution	Siena
Italy	Local Institution	Sondrio
Mexico	Local Institution	Acapulco	Guerrero
Mexico	Local Institution	Aguascalientes
Mexico	Local Institution	Cuernavaca	Morelos
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Mexico	Distrito Federal
Mexico	Local Institution	Puebla
Netherlands	Local Institution	Amsterdam
Netherlands	Local Institution	Mb Amsterdam
Peru	Local Institution	Arequipa
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Peru	Local Institution	Lima
Poland	Local Institution	Olsztyn
Puerto Rico	Ponce School Of Medicine	Ponce
Romania	Local Institution	Bucharest
Romania	Local Institution	Romania
Romania	Local Institution	Suceava
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Obninsk
Russian Federation	Local Institution	St Petersburg
Spain	Local Institution	Barcelona
Spain	Local Institution	Barcelona
Spain	Local Institution	Benidorm-alicante
Spain	Local Institution	Madrid
Spain	Local Institution	Santiago De Compostela
Spain	Local Institution	Valencia
United Kingdom	Local Institution	Cardiff	Glamorgan
United Kingdom	Local Institution	Chelmsford	Essex
United Kingdom	Local Institution	Manchester	Greater Manchester
United Kingdom	Local Institution	Nottingham	Nottinghamshire
United Kingdom	Local Institution	Scunthorpe	Lincolnshire
United States	Alaska Clinical Research Center, Llc	Anchorage	Alaska
United States	The Bunting-Blaustein Cancer Research Building	Baltimore	Maryland
United States	St. Luke'S Hospital & Health Network Laboratory	Bethlehem	Pennsylvania
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Gabrail Cancer Center	Canton	Ohio
United States	Musc Hollings Cancer Center	Charleston	South Carolina
United States	University Of Chicago	Chicago	Illinois
United States	University Of Cincinnati	Cincinnati	Ohio
United States	Center For Oncology Research & Treatment, P.A.	Dallas	Texas
United States	Cancer Care Specialists Of Central Illinois	Decatur	Illinois
United States	Highlands Oncology Group, P.A.	Fayetteville	Arkansas
United States	The Center For Cancer And Blood Disorders	Fort Worth	Texas
United States	Marsha G. Fink, Md, Inc.	Fountain Valley	California
United States	Frederick Memorial Hospital Regional Cancer Therapy Center	Frederick	Maryland
United States	Kentucky Cancer Clinic	Hazard	Kentucky
United States	Northwest Cancer Center	Houston	Texas
United States	The University Of Texas Md Anderson Cancer Center	Houston	Texas
United States	Edwards Comprehensive Cancer Center	Huntington	West Virginia
United States	Hutchinson Clinic, Pa	Hutchinson	Kansas
United States	University Of Iowa Hospitals And Clinics	Iowa City	Iowa
United States	Baptist Cancer Institute	Jacksonville	Florida
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	Suburban Hematology-Oncology Associates, Pc	Lawrenceville	Georgia
United States	Loma Linda University Cancer Center	Loma Linda	California
United States	Usc/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Prostate Oncology Specialists, Inc.	Marina Del Rey	California
United States	Southern Cancer Center	Mobile	Alabama
United States	Edward Cancer Center	Naperville	Illinois
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Mid-Illinois Hematology & Oncology Associates, Ltd	Normal	Illinois
United States	Orlando Health, Inc	Orlando	Florida
United States	Comprehensive Cancer Center	Palm Springs	California
United States	Va Pittsburgh Healthcare System	Pittsburgh	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Raleigh Hematology Oncology Associates	Raleigh	North Carolina
United States	Mayo Clinic	Rochester	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Va San Diego Healthcare System	San Diego	California
United States	Pacific Hematology Oncology Associates	San Francisco	California
United States	Siouxland Hematology-Oncology Assoc., Llp	Sioux City	Iowa
United States	St Johns Medical Research Institute, Inc.	Springfield	Missouri
United States	Arizona Clinical Research Center, Inc.	Tucson	Arizona
United States	Associates In Hematology & Oncology, P.C.	Upland	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czech Republic,  Denmark,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Mexico,  Netherlands,  Peru,  Poland,  Puerto Rico,  Romania,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	OS is defined as the time in months from randomization date to date of death due to any cause in all randomized subjects. For participants alive at the time of the database cutoff date, OS was censored at the last date the participant was known to be alive.	Randomization to date of death, up to November 2012, approximately 3.5 years	No
Secondary	Progression Free Survival (PFS)	All PFS events were based on investigator's assessment. Participants who were alive and did not experience a PFS event were censored at the earlier of the latest prostate-specific antigen (PSA) or radiological tumor assessment date. Participants who did not die, showed no clinical deterioration, and who had no recorded post-baseline PSA or radiological tumor assessment were censored at randomization date.	Date of randomization to earliest date of confirmed PSA or radiological progression, clinical deterioration or death, up to November 2012, approximately 3.5 years	No
Secondary	Pain Response	The percentage of participants with a pain response assessed using the Brief Pain Inventory Short Form (BPI-SF) completed by participants throughout the study in a daily diary log. Pain-evaluable participants were defined as those with a decrease in the average daily worst pain intensity by at least 30% from baseline, maintained over 2 consecutive evaluations without the use of any rescue analgesic medication or increase in analgesic use in the same time period.	Assessed at screening, weeks 12, 18, 24, and at the end of treatment visit	No
Secondary	Duration of Pain Response	The time between the initial date of pain response and completion date of pain response. The initial date when the pain response criterion was achieved was considered the pain response date. The earlier of date of death, date of tumor resection surgery, or date when pain response criterion was no longer met was considered the completion date of the pain response. If none of these scenarios occurred, the completion of the pain response was set to the last known alive date.	Day of initial pain response to day of completion of pain response or date of death	No
Secondary	Number of Participants With Severe Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs, Immune-Related Adverse Events (irAE) and Immune-Mediated Adverse Reaction (imAR)	AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.; SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during study and up to 70 days after last dose. IrAEs=AEs potentially associated with inflammation and considered to be causally related to study drug and grouped into gastrointestinal (GI), hepatic, skin, endocrine and neurological. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies. IrAEs/ imARs were graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.	Randomization to date of death, up to November 2012, approximately 3.5 years	Yes
Secondary	Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE)	The time between first dose of study drug and date of earliest Grade 3 or 4 irAE. These irAEs are AEs of unknown etiology, consistent with an immune phenomenon and considered as causally related to drug exposure. The five subcategories of irAE examined include gastrointestinal (GI), liver, skin, endocrine, and neurological and are graded using the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0.	Day 1 to 70 days after last dose of study drug	Yes
Secondary	Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE)	Time between the date of onset of a Grade 3 or 4 irAE and the date of improvement to Grade 1 or less or the worst grade at baseline.	Day 1 to 70 days after last dose of study drug	Yes
Secondary	Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR)	The time between first dose of study drug and date of earliest Grade 3 or 4 imAR. ImARs were collected prospectively and grouped into enterocolitis, hepatitis, dermatitis, neuropathies and endocrinopathies and graded using Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE), Ver. 3.0.; Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.	Day 1 to time of onset of the imAR of interest	Yes
Secondary	Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0	Time between the date of onset of an imAR to the date of resolution date of the event or the last known date participant was alive if an event did not resolve.; Only the Ipilimumab + Radiotherapy group of participants was included in the analysis because ipilimumab is associated with inflammatory events resulting from increased or excessive immune activity likely to be related to its mechanism of action.	Day 1 to 70 days after last dose of study drug	Yes
Secondary	Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline	Comparison of baseline versus worst grade hematology laboratory tests as measured by white blood count (WBC), absolute neutrophil count (ANC), platelet count, hemoglobin and lymphocyte results. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for WBC were based on Gr 1: 3.0 - < Lower Limit of Normal (LLN); Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0. Abnormal values for Hemoglobin were based on Gr 1: 10.0 - < LLN; Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5. Abnormal values for Lymphocytes were based on Gr 1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2. Abnormal values for ANC were based on Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5. Abnormal values for Platelets were based on Gr 1: 75.0 - < LLN; Gr 2: 50.0 - < 75.0; Gr 3: 25.0 - < 50.0; Gr 4: < 25.0.	Day 2 to 70 days after last dose of study drug	Yes
Secondary	Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline	Comparison of baseline versus worst grade liver function as measured by alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin and alkaline phosphatase (ALP). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for ALP, ALT and AST were based on grades; Gr 1: > 1.0 - 2.5 * upper limits of normal (ULN); Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN. Abnormal values for Total Bilirubin were based on Gr 1: > 1.0 - 1.5 * upper limits of normal (ULN); Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.	Day 2 to 70 days after last dose of study drug	Yes
Secondary	Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline	Comparison of baseline versus worst grade serum chemistry as measured by lipase and amylase analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr). Gr 0: within normal range. Abnormal values for lipase: Gr1: > 1.0 - 1.5 * ULN; Gr2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0*ULN. Abnormal values for amylase: Gr1: > 1.0 - 1.5 * ULN; Gr 2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0 * ULN.	Day 2 to 70 days after last dose of study drug	Yes
Secondary	Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline	Comparison of baseline versus worst grade renal function as measured by creatinine analysis. National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade (Gr).Gr 0: within normal range. Abnormal values for Creatinine were based on Gr 1: > 1.0 - 1.5*ULN; Gr 2: > 1.5 - 3.0*ULN; Gr 3: > 3.0 - 6.0*ULN; Gr 4: > 6.0*ULN.	Day 2 to 70 days after last dose of study drug	Yes

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