Clinical trial NCT00323882: Study of MDX-010 in Patients With Metastatic Hormone-Refractory Prostate Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Neoplasm Metastasis
Keywords: Prostate Cancer
Oncology
Prostate
Cancer
Metastatic
Hormone
PSA
Metastatic Hormone-Refractory Prostate Cancer (HRPC)
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-05-10
Enrollment: 75
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Serious AEs (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs - Treated Participants
timeFrame: Day 1 to last day of study treatment (+70 days) up to 2 years
measure: Number of Participants With Best PSA Response at Day 85 by Category - PSA Evaluable Participants
timeFrame: Day 85
Secondary outcomes:
measure: Number of Participants With Best Overall PSA Response by Category - PSA Evaluable Participants
timeFrame: Day 1 to last day of study treatment (+70 days) up to 2 years
measure: Number of Participants With Best Overall Tumor Response by Category - Tumor Evaluable Participants
timeFrame: Day 1 to last day of study treatment (+70 days) up to 2 years
measure: Time to PSA Response at Day 85 in Participants With Complete Response (CR) or Confirmed Partial Response (PR) at Day 85
timeFrame: Day 1 to Day 85
measure: Overall Tumor Response Rate in 10 mg/kg Ipilimumab Monotherapy and Ipilimumab/XRT Combination Therapy
timeFrame: Day 1 to last day of study treatment (+70 days) up to 2 years
measure: PSA Response Rate at Day 85 and Overall PSA Response Rate in 10 mg/kg Monotherapy and Combination Therapy
timeFrame: Day 85, Day 1 to last day of study treatment (+70 days) up to 2 years
measure: Number of Participants Who Died by Date of Primary Analysis and by Date of Completion of Follow Up - All Treated Participants
timeFrame: Day 1 to 5 years post treatment
measure: Overall Survival at Completion of Follow Up Period - Treated Participants
timeFrame: Day 1 to 5 years post treatment
measure: Number of Participants With On-Study Hematology Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants
timeFrame: Day 1 to last day of study treatment (+70 days) up to 2 years
measure: Number of Participants With On-Study Serum Chemistry Laboratory Tests Worst Common Terminology Criteria (CTC) Grade - Treated Participants
timeFrame: Day 1 to last day of study treatment (+70 days) up to 2 years
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities at Baseline and During Treatment Period - Treated Participants
timeFrame: Baseline up to 2 years
measure: Number of Participants Positive for Human Anti-Human Antibodies (HAHA) - Treated Participants
timeFrame: Day 1 up to 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Brownstown
country: United States
facility: Josephine Ford Cancer Center-Downriver
state: Michigan
city: Dearborn
country: United States
facility: Henry Ford Medical Center-Fairlane
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: West Bloomfield
country: United States
facility: Henry Ford Medical Center-West Bloomfield
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.