Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Vaccine Therapy, MDX-010, and GM-CSF in Treating Patients With Metastatic Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	NCI-05-C-0167 7207, NCI-7207, NCT00124670

Objectives

Primary

1. 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.
2. Determine the safety and tolerability of this regimen in these patients.

Secondary

1. 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.
2. Determine the clinical response, as measured by RECIST and PSA consensus criteria, in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed prostate cancer
  • Metastatic disease
  • Androgen-independent disease



• No bone pain requiring narcotics



• No brain metastases

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Lymphocyte count ≥ 500/mm³
• 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

Expected Enrollment

A maximum of 30 patients will be accrued for this study within 2-3 years.

Outcomes

Safety by CTCAE v 3.0

Objective responses by RECIST every 2 months
Prostate-specific antigen (PSA) response by monthly serum PSA
Compare immunologic responses by ELISPOT at baseline and day 99

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.

Gulley JL, Arlen PM, Madan R, et al.: Phase I trial of a PSA based vaccine and ipilimumab in patients (pts) with metastatic castrate resistant prostate cancer (CRPC). [Abstract] American Association for Cancer Research: Molecular Targets and Cancer Therapeutics, October 22-26, 2007, San Francisco, CA A-142, 2007.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

James Gulley, MD, PhD, Principal investigator		Ph: 301-435-2956 Email: gulleyj@mail.nih.gov

Related Information

Web site for additional information

Registry Information
Official Title		Phase I Trial of a PSA Based Vaccine and an Anti-CTLA-4 Antibody in Adults with Metastatic Androgen Independent Prostate Cancer
Trial Start Date		2005-06-06
Trial Completion Date		2007-02-26 (estimated)
Registered in ClinicalTrials.gov		NCT00124670
Date Submitted to PDQ		2005-06-15
Information Last Verified		2008-04-06

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