Study of Immunotherapy to Treat Advanced Prostate Cancer
- Registration Number
- NCT00861614
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of the study is to determine if advanced prostate cancer patients that are treated with radiotherapy (RT) plus ipilimumab live longer that those treated with RT alone
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 988
- Advanced prostate cancer
- At least 1 bone metastasis
- Testosterone < 50 ng/dl
- Prior treatment with docetaxel
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Ipilimumab Ipilimumab -
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Date of randomization to date of death 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.
Overall Survival Rate Date of randomization to date of death The overall survival (OS) rate is a percentage, representing the fraction of all randomized participants who were alive following treatment, from 1 to 5 years. OS was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) Date of randomization to earliest date of confirmed PSA or radiological progression, clinical deterioration or death 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.
Pain Response Assessed at screening, weeks 12, 18, 24, and at the end of treatment visit 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.
Duration of Pain Response Day of initial pain response to day of completion of pain response or date of death 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.
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) Randomization to date of death 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.Time to Onset of Grade 3 or 4 Immune-Related Adverse Event (irAE) Day 1 to 70 days after last dose of study drug 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.
Time to Resolution of Grade 3 or 4 Immune-Related Adverse Event (irAE) Day 1 to 70 days after last dose of study drug 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.
Time to Onset of Grade 3 to 5 Immune-Mediated Adverse Reaction (imAR) Day 1 to time of onset of the imAR of interest 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.Time to Resolution of Grade 3 to 5 to Grade 0 Immune-Mediated Adverse Reactions (imARs) to Grade 0 Day 1 to 70 days after last dose of study drug 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.Number of Participants With Worst On-Study Hematology Common Toxicity Criteria (CTC) Grade and Shift From Baseline Day 1 to 70 days after last dose of study drug 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.
Number of Participants With Worst On-Study Liver Common Toxicity Criteria (CTC) Grade and Shift From Baseline Day 1 to 70 days after last dose of study drug 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.
Number of Participants With Worst On-Study Serum Chemistry Common Toxicity Criteria (CTC) Grade and Shift From Baseline Day 1 to 70 days after last dose of study drug 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.
Number of Participants With Worst On-Study Renal Function Common Toxicity Criteria (CTC) Grade and Shift From Baseline Day 1 to 70 days after last dose of study drug 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.
Trial Locations
- Locations (46)
Southern Cancer Center
🇺🇸Mobile, Alabama, United States
Arizona Clinical Research Center, Inc.
🇺🇸Tucson, Arizona, United States
Loma Linda University Cancer Center
🇺🇸Loma Linda, California, United States
Prostate Oncology Specialists, Inc.
🇺🇸Marina Del Rey, California, United States
Comprehensive Cancer Center
🇺🇸Palm Springs, California, United States
Baptist Cancer Institute
🇺🇸Jacksonville, Florida, United States
Orlando Health, Inc
🇺🇸Orlando, Florida, United States
Marsha G. Fink, Md, Inc.
🇺🇸Fountain Valley, California, United States
Usc/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University Of Chicago
🇺🇸Chicago, Illinois, United States
Va Pittsburgh Healthcare System
🇺🇸Pittsburgh, Pennsylvania, United States
The University Of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Suburban Hematology-Oncology Associates, Pc
🇺🇸Lawrenceville, Georgia, United States
Cancer Care Specialists Of Central Illinois
🇺🇸Decatur, Illinois, United States
Edward Cancer Center
🇺🇸Naperville, Illinois, United States
Mid-Illinois Hematology & Oncology Associates, Ltd
🇺🇸Normal, Illinois, United States
University Of Iowa Hospitals And Clinics
🇺🇸Iowa City, Iowa, United States
St. Luke'S Hospital & Health Network Laboratory
🇺🇸Bethlehem, Pennsylvania, United States
Va San Diego Healthcare System
🇺🇸San Diego, California, United States
Pacific Hematology Oncology Associates
🇺🇸San Francisco, California, United States
University Of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Highlands Oncology Group, P.A.
🇺🇸Fayetteville, Arkansas, United States
Alaska Clinical Research Center, Llc
🇺🇸Anchorage, Alaska, United States
Ponce School Of Medicine
🇵🇷Ponce, Puerto Rico
Local Institution
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Musc Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Edwards Comprehensive Cancer Center
🇺🇸Huntington, West Virginia, United States
The Bunting-Blaustein Cancer Research Building
🇺🇸Baltimore, Maryland, United States
Raleigh Hematology Oncology Associates
🇺🇸Raleigh, North Carolina, United States
Siouxland Hematology-Oncology Assoc., Llp
🇺🇸Sioux City, Iowa, United States
Frederick Memorial Hospital Regional Cancer Therapy Center
🇺🇸Frederick, Maryland, United States
Hutchinson Clinic, Pa
🇺🇸Hutchinson, Kansas, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Kentucky Cancer Clinic
🇺🇸Hazard, Kentucky, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Kansas City Veterans Affairs Medical Center
🇺🇸Kansas City, Missouri, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States
Associates In Hematology & Oncology, P.C.
🇺🇸Upland, Pennsylvania, United States
The Center For Cancer And Blood Disorders
🇺🇸Fort Worth, Texas, United States
Center For Oncology Research & Treatment, P.A.
🇺🇸Dallas, Texas, United States
St Johns Medical Research Institute, Inc.
🇺🇸Springfield, Missouri, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Northwest Cancer Center
🇺🇸Houston, Texas, United States