Study of MDX-010 in Patients With Metastatic Hormone-Refractory Prostate Cancer

NCT00323882 | Completed Phase 1 Results

• 2 other identifiers: CA184-017 STCA184-017
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 14

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.

Conditions

Prostate Cancer; Neoplasm Metastasis

Keywords

Prostate Cancer; Oncology; Prostate; Cancer; Metastatic; Hormone; PSA; Metastatic Hormone-Refractory Prostate Cancer (HRPC)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Serious AEs (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Immune-related AEs - Treated Participants

  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.

  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

  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 Outcomes (11)

• Number of Participants With Best Overall PSA Response by Category - PSA Evaluable Participants

  Day 1 to last day of study treatment (+70 days) up to 2 years

• Number of Participants With Best Overall Tumor Response by Category - Tumor Evaluable Participants

  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

  Day 1 to Day 85

• Overall Tumor Response Rate in 10 mg/kg Ipilimumab Monotherapy and Ipilimumab/XRT Combination Therapy

  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

  Day 85, Day 1 to last day of study treatment (+70 days) up to 2 years

Study Arms (1)

MDX-010

EXPERIMENTAL

Drug: MDX-010

Interventions

MDX-010 DRUG

selected dose administered IV every 3 weeks

MDX-010

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (14)

The Angeles Clinic and Research Institute

Los Angeles, California, 11818, United States

Location

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Josephine Ford Cancer Center-Downriver

Brownstown, Michigan, 48183, United States

Location

Henry Ford Medical Center-Fairlane

Dearborn, Michigan, 48126, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202-2689, United States

Location

Henry Ford Medical Center-West Bloomfield

West Bloomfield, Michigan, 48322, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (3)

• 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.

  PMID: 34435699 DERIVED

• 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.

  PMID: 24695685 DERIVED

• 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.

  PMID: 23535954 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis; Neoplasms

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Due to the small number of participants who underwent more than 4 doses of treatment (induction period) and the exploratory nature of this study, not all of the secondary objectives were completed.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2006
• First Posted: May 10, 2006
• Study Start: January 1, 2006
• Primary Completion: September 1, 2009
• Study Completion: July 1, 2013
• Last Updated: August 28, 2014
• Results First Posted: August 28, 2014

Record last verified: 2014-08

Locations

US (14)