Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Monoclonal Antibody and Sargramostim in Treating Patients With Metastatic Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active 18 and over NCI UCSF-02558 NCI-6032, NCT00064129, 6032

Objectives

1. Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) administered with sargramostim (GM-CSF) in patients with metastatic androgen-independent prostate cancer.
2. Determine the safety of this regimen in these patients.
3. Determine the T-cell immunity and T-cell response in patients treated with this regimen.
4. Determine the pharmacokinetics of MDX-010 in these patients.
5. Determine the prostate-specific antigen and/or objective responses in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed prostate cancer
  • Metastatic disease



• Progressive disease after prior androgen deprivation as defined by at least 1 of the following criteria:
  • Patients with measurable disease must have an increase of at least 20% in the sum of the longest diameter of target lesions OR the appearance of 1 or more new lesions
  • Patients with nonmeasurable disease must have a positive bone scan and a prostate-specific antigen (PSA) level of at least 5 ng/mL, which has risen on at least 2 successive occasions at least 2 weeks apart*
    • At least 1 PSA level must be obtained at least 4 weeks after flutamide (6 weeks after bicalutamide or nilutamide)

   [Note: *An additional PSA level is required if the confirmatory PSA is not greater than the screening PSA]




• Testosterone no greater than 50 ng/dL
  • Patients with no prior orchiectomy must continue luteinizing hormone-releasing hormone agonist therapy



• No history or radiologic evidence of CNS metastases

Prior/Concurrent Therapy:

Biologic therapy

• No prior immunotherapy (e.g., vaccines or investigational)
• No other concurrent colony-stimulating factors

Chemotherapy

• No prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior systemic corticosteroids
• At least 4 weeks since other prior hormonal therapy, including megestrol and finasteride
• No concurrent systemic steroid therapy except inhaled or topical steroids
• No other concurrent hormonal therapy
  • Hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• More than 8 weeks since prior radiopharmaceuticals (e.g., strontium chloride Sr 89 and samarium Sm 153 lexidronam pentasodium)
• Prior irradiation of a symptomatic lesion or one that may produce disability (e.g., unstable femur) allowed
• No concurrent palliative radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 4 weeks since prior herbal products known to decrease PSA levels (e.g., PC-SPES or saw palmetto)

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 8 g/dL

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No significant cardiovascular disease
• No New York Heart Association class III or IV congestive heart failure
• No active angina pectoris
• No myocardial infarction within the past 6 months

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception prior to, during, and for 3 months after study participation
• No history of autoimmune disease including, but not limited to, any of the following:
  • Systemic lupus erythematosus
  • Rheumatoid arthritis
  • Inflammatory bowel disease
• No other medical or psychiatric illness that would preclude study participation or giving informed consent
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer currently in complete remission

Expected Enrollment

A total of 12-24 patients will be accrued for this study within 6-7 months.

Outline

This is a multicenter, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010).

Patients receive MDX-010 IV over 90 minutes on day 1 and sargramostim (GM-CSF) subcutaneously on days 1-14. Treatment repeats every 28 days for a total of 4 courses. GM-CSF continues beyond 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MDX-010 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 30 days.

Trial Contact Information

Trial Lead Organizations

UCSF Helen Diller Family Comprehensive Cancer Center

Eric Small, MD, Protocol chair		Ph: 415-353-7095; 800-888-8664

U.S.A.
California
	San Francisco
	UCSF Helen Diller Family Comprehensive Cancer Center
		Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center	Ph:  877-827-3222
	Veterans Affairs Medical Center - San Francisco
		H. Jeffrey Lawrence, MD	Ph:  415-379-5615
			Email: jeffl@medicine.ucsf.edu

Registry Information
Official Title		A Phase I Study of Repetitive Dosing of Anti-CTLA-4 Antibody (MDX-010) in Combination with GM-CSF in Patients with Metastatic, Androgen-Independent Prostate Cancer
Trial Start Date		2003-05-13
Trial Completion Date		2003-11-29 (estimated)
Registered in ClinicalTrials.gov		NCT00064129
Date Submitted to PDQ		2003-05-22
Information Last Verified		2006-12-05
NCI Grant/Contract Number		CA82103

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