- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00323882
Study of MDX-010 in Patients With Metastatic Hormone-Refractory Prostate Cancer
August 14, 2014 updated by: Bristol-Myers Squibb
A Phase I/II, Open-label, Dose-escalation Study of MDX-010 Administered Every 3 Weeks for 4 Doses in Patients With Metastatic Hormone-Refractory Prostate Cancer
Multicenter study in which patients with metastatic hormone refractory prostate cancer (HRPC), who have not had previous chemotherapy or immunotherapy treatments, received MDX-010 every 3 weeks for 4 doses (12 weeks total duration of induction).
MDX-010 was administered at escalating dosage levels of 3, 5, and 10 mg/kg/dose infusions.
At least 6 patients were to be enrolled in each dosage level.
Patients who tolerated and responded to treatment or who had stable disease for 3 months or longer and who subsequently progressed during the follow up phase of the study had the option to receive additional treatment with MDX-010, up to 4 cycles.
Patients were followed in the study for response up to 2 years and were followed for survival status for up to 5 years after enrollment.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
75
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90025
- The Angeles Clinic and Research Institute
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Los Angeles, California, United States, 11818
- The Angeles Clinic and Research Institute
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San Francisco, California, United States, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University School of Medicine
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Michigan
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Brownstown, Michigan, United States, 48183
- Josephine Ford Cancer Center-Downriver
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Dearborn, Michigan, United States, 48126
- Henry Ford Medical Center-Fairlane
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Detroit, Michigan, United States, 48202-2689
- Henry Ford Hospital
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West Bloomfield, Michigan, United States, 48322
- Henry Ford Medical Center-West Bloomfield
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Missouri
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St. Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New York
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New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
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North Carolina
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Huntersville, North Carolina, United States, 28078
- Carolina BioOncology Institute
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Oregon
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Portland, Oregon, United States, 97239-3098
- Oregon Health and Science University
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Washington
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Seattle, Washington, United States, 98109
- Seattle Cancer Care Alliance
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Seattle, Washington, United States, 98195
- University of Washington Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- Histologic diagnosis of adenocarcinoma of the prostate
- Metastatic prostate cancer (positive bone scan or measurable disease)
- Total testosterone of less than 50 ng/dL, except for patients with prior orchiectomy, where testosterone does not need to be measured.
- Patients who are receiving an antiandrogen as part of primary androgen ablation must demonstrate disease progression following discontinuation of antiandrogen and completion of a washout period and then observe disease progression.
- Patients must stop using any herbal product known to decrease PSA levels (eg., saw palmetto and PC-SPES) or any systemic or topical corticosteroid at least 4 weeks prior to screening. Progressive disease must be documented after discontinuation of these products.
- Progressive disease after androgen deprivation (or hormone therapy). For patients with measurable disease, progression will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. For patients with progression in, or without any measurable disease, a positive bone scan and elevated PSA will be required.
- Patients receiving bisphosphate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to enrollment.
- No prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control prostate cancer).
- Prior radiation therapy completed at least 4 weeks prior to enrollment. No prior radiopharmaceuticals (strontium, samarium) within 8 weeks prior to enrollment.
Exclusion Criteria:
- Bone pain due to metastatic bone disease severe enough to require routine narcotic analgesic use.
- History of severe hypersensitivity reactions to drugs formulated with polysorbate 80.
- Patients with active autoimmune disease or a history of autoimmune disease that required systemic steroids or immunosuppressive medications, except for patients with vitiligo.
- Prior therapy with any anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibody.
- Active infection requiring therapy.
- Concurrent medical condition requiring the use of systemic or topical corticosteroids; systemic or topical corticosteroids must be discontinued at least 4 weeks prior to enrollment. The use of inhaled corticosteroids is acceptable.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: MDX-010
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selected dose administered IV every 3 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Serious AEs (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs - Treated Participants
Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years
|
AEs graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
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.
Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling, Gr 5=Death.
Related=relationship to study drug reported as certain, probable, possible, or missing.
Immune-related AE (irAE) was defined as a clinically significant AE of any organ that is associated with drug exposure, of unknown etiology, and is consistent with an immune-mediated mechanism.
Day 1=first day of study treatment.
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Day 1 to last day of study treatment (+70 days) up to 2 years
|
Number of Participants With Best PSA Response at Day 85 by Category - PSA Evaluable Participants
Time Frame: Day 85
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Response by investigator using National Cancer Institute (NCI) PSA Working Group recommendations= PSA < 50% of PSA reference value occurring on or before Day 85; response confirmed at least 4 weeks after the first measurement.
PSA reference=PSA measured immediately prior to treatment.
Complete response (CR)=PSA < 2 nanograms per milliliter (ng/mL), confirmed at least 4 weeks after 1st value; Partial response (PR)=PSA ≤ 50% of PSA reference, confirmed at least 4 weeks after 1st value; Unconfirmed=not confirmed by repeat measurements; Stable disease(SD)=No change from PSA reference; Progressive disease (PD) defined: If PSA nadir was ≥ 100% of the reference: PSA ≥ 125% of PSA reference and with a difference of absolute value of ≥ 5 ng/mL; If PSA nadir was < 100% and ≥ 50% of the reference: PSA ≥ 125% of PSA nadir and with a difference of absolute value of ≥ 5 ng/mL: If PSA nadir was < 50% of the reference: PSA ≥ 150% of PSA nadir and with a difference of absolute value of ≥ 5 ng/mL.
|
Day 85
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Best Overall PSA Response by Category - PSA Evaluable Participants
Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years
|
Best Overall PSA response per investigator, using NCI PSA Working Group: PSA with CR or PR at any time after treatment initiation and was confirmed at least 4 weeks after the first measurement.
PSA reference=PSA measured immediately prior to treatment.
CR=PSA concentration < 2 nanograms per milliliter (ng/mL), confirmed at least 4 weeks after 1st value; PR=PSA concentration ≤ 50% of PSA reference, confirmed at least 4 weeks after 1st value; Unconfirmed=not confirmed by repeat measurements; SD=No change from PSA reference value; PD = If PSA nadir was ≥ 100% of the reference value: PSA ≥ 125% of PSA reference and with a difference of absolute value of ≥ 5 ng/mL; If PSA nadir was < 100% and ≥ 50% of the reference value: PSA ≥ 125% of PSA nadir and with a difference of absolute value of ≥ 5 ng/mL: If PSA nadir was < 50% of the reference value: PSA ≥ 150% of PSA nadir and with a difference of absolute value of ≥ 5 ng/mL.
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Day 1 to last day of study treatment (+70 days) up to 2 years
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Number of Participants With Best Overall Tumor Response by Category - Tumor Evaluable Participants
Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years
|
For those with measurable disease, tumor response based upon tumor lesions (per investigator) using Response Evaluation Criteria in Solid Tumors (RECIST).
Best Overall=Participants with a best tumor response of CR or PR at anytime during the study.
CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference, baseline sum LD.
For a status of CR or PR, changes in tumor measurements were confirmed by repeat studies no less than 4 weeks after the criteria for response were first met; Unconfirmed=not confirmed by repeat measurements; SD=Neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
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Day 1 to last day of study treatment (+70 days) up to 2 years
|
Time to PSA Response at Day 85 in Participants With Complete Response (CR) or Confirmed Partial Response (PR) at Day 85
Time Frame: Day 1 to Day 85
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Time to PSA response was measured in months.
Time to PSA response was analyzed in those participants with CR or PR at Day 85. CR=PSA concentration < 2 ng/mL, confirmed at least 4 weeks after 1st value; PR=PSA concentration ≤ 50% of PSA reference, confirmed at least 4 weeks after 1st value.
|
Day 1 to Day 85
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Overall Tumor Response Rate in 10 mg/kg Ipilimumab Monotherapy and Ipilimumab/XRT Combination Therapy
Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years
|
Tumor response rate was defined as the number of participants with a best response of partial or complete response divided by the total number of tumor evaluable participants.
Overall Tumor Response was defined as participants with a tumor response of CR or PR at anytime during the study.
CR=Disappearance of all target lesions; PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference, baseline sum LD.
For a status of CR or PR, changes in tumor measurements were confirmed by repeat studies no less than 4 weeks after the criteria for response were first met
|
Day 1 to last day of study treatment (+70 days) up to 2 years
|
PSA Response Rate at Day 85 and Overall PSA Response Rate in 10 mg/kg Monotherapy and Combination Therapy
Time Frame: Day 85, Day 1 to last day of study treatment (+70 days) up to 2 years
|
PSA response rate was defined as the number of participants with a PSA response (PR or CR) divided by the total number of PSA evaluable participants.
PSA response at Day 85, as reported by the investigator, was defined as a PSA concentration < 50% of the PSA reference value occurring on or before Day 85 and this response was confirmed at least 4 weeks after the first determination.
The PSA reference value was the PSA concentration measured immediately prior to treatment.
Overall Response is < 50% of the PSA reference value occurring anytime after treatment was initiated and this response was confirmed at least 4 weeks after the first determination.
Complete response=PSA concentration < 2 ng/mL, confirmed at least 4 weeks after first value; Partial response=PSA concentration ≤ 50% of PSA reference value, confirmed at least 4 weeks after first determination.
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Day 85, Day 1 to last day of study treatment (+70 days) up to 2 years
|
Number of Participants Who Died by Date of Primary Analysis and by Date of Completion of Follow Up - All Treated Participants
Time Frame: Day 1 to 5 years post treatment
|
Primary analysis was conducted on data from Day 1 up to 2 years post treatment, data available as of September 2009.
Final Follow-Up analysis was conducted on data up to 5 years post treatment, data available as of September 2013 (minimum time of eligibility 54 months to a maximum of 85 months).
Primary causes of deaths are listed under each timepoint.
|
Day 1 to 5 years post treatment
|
Overall Survival at Completion of Follow Up Period - Treated Participants
Time Frame: Day 1 to 5 years post treatment
|
Overall Survival (OS) was defined as the time from the first date of study treatment until the date of death and was measured in months.
For those participants who have not died, OS was censored at the last date the participant was known to be alive.
Completion of follow-up for OS was a minimum time of eligibility 54 months to a maximum of 85 months.
|
Day 1 to 5 years post treatment
|
Number of Participants With On-Study Hematology Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants
Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years
|
NCI CTC version(v) 3.0 was used to determine Grade (Gr).
Screening was Day -28 to Day -1.
On-study laboratories were reported after the first dose date, every 21 days during a treatment cycle, and within 70 days of last dose of study therapy (ie, Days 1, 22, 43, 64, 85, etc).
Hemoglobin grams per liter (g/L): Gr 1: 10.0 - less than (<) lower limit of normal (LLN); Gr 2: 8.0 - < 10.0; Gr 3: 6.5 - < 8.0; Gr 4: < 6.5.
White blood cells(WBC) 10^9 cells per liter (c/L): Gr1: 3.0 - < LLN; Gr 2: 2.0 - < 3.0; Gr 3: 1.0 - < 2.0; Gr4: < 1.0.
Lymphocytes (absolute) 10^9 c/L: Gr1: 0.8 - < 1.5; Gr 2: 0.5 - < 0.8; Gr 3): 0.2 - < 0.5; Gr 4: < 0.2.
Neutrophils (absolute) 10^9 c/L: Gr 1: 1.5 - < 2.0; Gr 2: 1.0 - < 1.5; Gr 3: 0.5 - < 1.0; Gr 4: < 0.5.
Platelets 10^9 c/L: Gr 1: 75.0 - < lower limits of normal (LLN); Gr 2: 50.0 - < 75.0;
Gr 3: 25.0 - < 50.0;
Gr 4: < 25.0.
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Day 1 to last day of study treatment (+70 days) up to 2 years
|
Number of Participants With On-Study Serum Chemistry Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants
Time Frame: Day 1 to last day of study treatment (+70 days) up to 2 years
|
CTC v3.0 used.
On-study serum chemistry laboratories were reported after first dose date, every 21 days during a treatment cycle, and within 70 days of last dose of study therapy (ie, Days 1, 22, 43, 64, 85, etc).
Alanine Aminotransferase (ALT) Units per Liter (U/L) 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.
Aspartate Aminotransferase (AST) U/L: Gr 1: > 1.0 - 2.5 * ULN; Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN.
Total Bilirubin micromoles per liter (µmol/L): Gr 1: > 1.0 - 1.5 * ULN; Gr 2: > 1.5 - 3.0 * ULN; Gr 3: > 3.0 - 10.0 * ULN; Gr 4: > 10.0 * ULN.
Alkaline Phosphatase U/L: Gr 1: > 1.0 - 2.5 * ULN; Gr 2: > 2.5 - 5.0 * ULN; Gr 3: > 5.0 - 20.0 * ULN; Gr 4: > 20.0 * ULN.
Amylase U/L: Gr1: > 1.0 - 1.5 * ULN; Gr 2: > 1.5 - 2.0 * ULN; Gr 3: > 2.0 - 5.0 * ULN; Gr4: > 5.0 * ULN.
Creatinine µmol/L: Gr1: > 1.0 - 1.5*ULN; Gr2: > 1.5 - 3.0*ULN; Gr3: > 3.0 - 6.0*ULN; Gr4: > 6.0*ULN.
|
Day 1 to last day of study treatment (+70 days) up to 2 years
|
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities at Baseline and During Treatment Period - Treated Participants
Time Frame: Baseline up to 2 years
|
12 Lead Electrocardiograms (ECGs) were performed at screening (Day -28 to Day -1), and on Day 85 during a treatment cycle, and at the end of treatment period.
Clinically significant abnormalities could include atrial fibrillation, anterior fascicular block, marked sinus bradycardia, possible lateral infarct, and T-wave abnormality (other potential abnormalities were not excluded from consideration).
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Baseline up to 2 years
|
Number of Participants Positive for Human Anti-Human Antibodies (HAHA) - Treated Participants
Time Frame: Day 1 up to 2 years
|
HAHA was measured by electrochemiluminescent (ECL) immunoassay for the detection of antibodies in human heparin plasma.
Testing was performed on Days 1 (prior to ipilimumab infusion), 64, 85, and at completion of treatment.
|
Day 1 up to 2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Sun BL. Immunotherapy in treatment of metastatic prostate cancer: An approach to circumvent immunosuppressive tumor microenvironment. Prostate. 2021 Nov;81(15):1125-1134. doi: 10.1002/pros.24213. Epub 2021 Aug 26.
- Iwama S, De Remigis A, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014 Apr 2;6(230):230ra45. doi: 10.1126/scitranslmed.3008002.
- Slovin SF, Higano CS, Hamid O, Tejwani S, Harzstark A, Alumkal JJ, Scher HI, Chin K, Gagnier P, McHenry MB, Beer TM. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013 Jul;24(7):1813-1821. doi: 10.1093/annonc/mdt107. Epub 2013 Mar 27.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2006
Primary Completion (Actual)
September 1, 2009
Study Completion (Actual)
July 1, 2013
Study Registration Dates
First Submitted
May 8, 2006
First Submitted That Met QC Criteria
May 8, 2006
First Posted (Estimate)
May 10, 2006
Study Record Updates
Last Update Posted (Estimate)
August 28, 2014
Last Update Submitted That Met QC Criteria
August 14, 2014
Last Verified
August 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Neoplastic Processes
- Prostatic Neoplasms
- Neoplasm Metastasis
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Ipilimumab
Other Study ID Numbers
- CA184-017 ST
- CA184-017 (Other Identifier: BMS)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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