Expired Study
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Bethesda, Maryland 20892


RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Biological therapies, such as MDX-010 and GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with MDX-010 and GM-CSF may be an effective treatment for prostate cancer. PURPOSE: This phase I trial is studying the side effects and best dose of MDX-010 when given together with vaccine therapy and GM-CSF in treating patients with metastatic prostate cancer.

Study summary:

OBJECTIVES: Primary - Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) when given with sargramostim (GM-CSF) and vaccine therapy comprising vaccinia-PSA-TRICOM vaccine and fowlpox-PSA-TRICOM vaccine in patients with androgen-independent metastatic prostate cancer. - Determine the safety and tolerability of this regimen in these patients. Secondary - Determine immunologic response, as measured by an increase in prostate-specific antigen (PSA) specific T-cells by ELISPOT assay, in HLA-A2-positive patients treated with this regimen. - Determine the clinical response, as measured by RECIST and PSA consensus criteria, in patients treated with this regimen. OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010). Patients receive a priming vaccination with vaccinia-PSA-TRICOM vaccine subcutaneously (SC) on day 1 and sargramostim (GM-CSF) SC on days 1-4. Patients then receive booster vaccinations with fowlpox-PSA-TRICOM vaccine SC and MDX-010 IV over 90 minutes on days 15, 43, 71, 99, 127, and 155. Patients also receive GM-CSF SC on days 15-18, 43-46, 71-74, 99-102, 127-130, and 155-158. Patients without disease progression after day 155 may continue to receive fowlpox-PSA-TRICOM vaccine and GM-CSF every 28 days 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 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed at 4 weeks and then annually for 15 years. PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 2-3 years.


DISEASE CHARACTERISTICS: - Histologically confirmed prostate cancer - Metastatic disease - Androgen-independent disease - No bone pain requiring narcotics - No brain metastases PATIENT CHARACTERISTICS: Age - 18 and over Performance status - ECOG 0-1 Life expectancy - At least 6 months Hematopoietic - Granulocyte count ≥ 1,500/mm^3 - Platelet count ≥ 100,000/mm^3 - Lymphocyte count ≥ 500/mm^3 - Hemoglobin ≥ 9 g/dL Hepatic - AST and ALT ≤ 2.5 times upper limit of normal - Bilirubin ≤ 1.5 mg/dL (total bilirubin ≤ 3.0 mg/dL for patients with Gilbert's syndrome) - Hepatitis B negative - Hepatitis C negative Renal - Creatinine clearance ≥ 60 mL/min - No proteinuria ≥ grade 2 (unless the cause is determined to be nonrenal) Cardiovascular - No history of congestive heart failure OR objective evidence of congestive heart failure by physical exam or imaging - No New York Heart Association class II-IV cardiac disease Pulmonary - No pulmonary disease with fatigue or dyspnea during ordinary physical activity Gastrointestinal - No inflammatory bowel disease - No Crohn's disease - No ulcerative colitis - No active diverticulitis Immunologic - HIV negative - No history of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia regimen - No serious hypersensitivity reaction to egg products - No autoimmune disease that requires treatment, including any of the following: - Addison's disease - Hashimoto's thyroiditis - Systemic lupus erythematosus - Sjögren's syndrome - Scleroderma - Goodpasture's syndrome - Active Graves disease - Autoimmune hemolytic anemia - Ulcerative and hemorrhagic colitis - Endocrine disorders (e.g., thyroiditis, hyperthyroidism, hypothyroidism, autoimmune hypophysitis/hypopituitarism, or adrenal insufficiency) - Sarcoid granuloma - Myasthenia gravis - Polymyositis - Guillain-Barre syndrome - History of autoimmunity allowed provided it has not required systemic immunosuppressive therapy OR does not threaten vital organ function, including the CNS, heart, lungs, kidneys, skin, and gastrointestinal tract - No history of multiple sclerosis - No immunodeficiency or immunosuppression (by disease or therapy) - No history of or active eczema or other eczematoid skin disorder - No other acute, chronic, or exfoliative skin condition, including any of the following: - Atopic dermatitis - Burns - Impetigo - Varicella zoster - Severe acne - Other open rashes or wounds Other - Fertile patients must use effective contraception during and for ≥ 4 months after completion of study treatment - No history of seizures - No history of encephalitis - No other active malignancy within the past 12 months except nonmelanoma skin cancer or carcinoma in situ of the bladder - No life-threatening illness - Able to avoid close household contact with the following individuals for ≥ 3 weeks after vaccination: - Individuals with prior or active eczema or other eczematoid skin disorder - Individuals with other acute, chronic, or exfoliative skin condition, including any of the following: - Atopic dermatitis - Burns - Impetigo - Varicella zoster - Severe acne - Other open rashes or wounds - Children 3 years of age or younger - Pregnant or nursing women - Immunodeficient or immunosuppressed individuals (by disease or therapy), including HIV-infected individuals - No other serious medical illness that requires treatment and would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy - Prior vaccinia immunization allowed - No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) - No other concurrent anticancer immunotherapy Chemotherapy - See Disease Characteristics - No prior chemotherapy - No concurrent chemotherapy Endocrine therapy - More than 2 weeks since prior and no concurrent systemic or topical steroids, including steroid eye drops - Nasal or inhaled steroids allowed - Concurrent gonadotropin-releasing hormone agonist or antagonist therapy required for patients who have not undergone prior bilateral surgical orchiectomy - No concurrent anticancer systemic glucocorticoids - Concurrent replacement glucosteroids for patients with pituitary insufficiency allowed - Concurrent steroids for therapy-induced autoimmunity allowed Radiotherapy - No concurrent anticancer radiotherapy Surgery - See Endocrine therapy - Recovered from prior surgery - No prior splenectomy - No concurrent major surgery for treatment of cancer Other - Recovered from prior therapy



Primary Contact:

Principal Investigator
James L. Gulley, MD, PhD, FACP
National Cancer Institute (NCI)

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

There is no listed contact information for this specific location.

Site Status: N/A

Data Source: ClinicalTrials.gov

Date Processed: October 09, 2019

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