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

Alternate Title

Vaccine Therapy and Sargramostim Compared With Empty Vector Control in Treating Patients With Metastatic Androgen-Independent Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	UCLA-0309014 THERION-TBC-PRO-002, NCT00078585

Objectives

1. Compare the safety and efficacy of vaccinia-PSA-TRICOM vaccine and fowlpox-PSA-TRICOM vaccine plus sargramostim (GM-CSF) vs empty vector control and placebo in patients with metastatic androgen-independent prostate cancer.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the prostate
  • Metastatic disease confirmed by 1 of the following:
    • Lymph node metastasis measurable by CT scan
    • Bone metastasis evaluable by bone scan



• Refractory to hormonal therapy
  • Evidence of 2 consecutive increases in prostate-specific antigen (PSA) documented at least 1 week apart, with 1 value at least 5 ng/mL



• Prior small pox vaccination confirmed by 1 or more of the following:
  • Scar at the vaccination site
  • Patient verbalization
  • Written documentation
  • Prior military service



• Castrate testosterone levels < 50 ng/dL, consistent with orchiectomy or continuous gonadotropin-releasing hormonal therapy (e.g., leuprolide or goserelin)



• Gleason score ≤ 7 (at initial diagnosis)



• No metastases to organs other than lymph nodes and bone

Prior/Concurrent Therapy:

Biologic therapy

• No prior biologic therapy or immunotherapy for cancer
• No other concurrent biologic therapy or immunotherapy for cancer

Chemotherapy

• No prior chemotherapy for prostate cancer
• No concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 28 days since prior systemic corticosteroid therapy (except inhaled or topical steroids)
• More than 42 days since prior antiandrogen therapy (e.g., bicalutamide, nilutamide, or flutamide)
• More than 42 days since other prior hormonal therapy (e.g., ketoconazole)
• No concurrent systemic steroid use

Radiotherapy

• More than 28 days since prior radiotherapy
• No concurrent palliative radiotherapy
• No concurrent strontium chloride Sr 89 therapy

Surgery

• See Disease Characteristics
• No prior splenectomy

Other

• More than 28 days since prior investigational therapy
• Concurrent bisphosphonate therapy allowed provided treatment was initiated at least 28 days prior to vaccination and remains at a constant level throughout study period
• No concurrent immunosuppressive therapy
• No concurrent opioid analgesics for tumor-associated pain

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute lymphocyte count ≥ 600/mm³
• Platelet count > 100,000/mm³
• WBC > 2,000/mm³
• Hemoglobin ≥ 10 g/dL

Hepatic

• AST < 4 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C surface antigen negative
• Bilirubin < 2.0 mg/dL

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• No significant cardiovascular abnormalities or diseases
• No New York Heart Association class III or IV congestive heart failure
• No myocardial infarction within the past 6 months
• No unstable angina
• No coronary angioplasty within the past 6 months
• No uncontrolled atrial or ventricular arrhythmias

Immunologic

• HIV negative
• No evidence of immunodeficiency or immune suppression
• No autoimmune disease, including the following:
  • Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
  • Systemic lupus erythematosus
  • Sjögren's syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Addison's disease
  • Hashimoto's thyroiditis
  • Active Graves disease
• No allergy or untoward reaction to prior vaccinia (smallpox) vaccination
• No allergy or untoward reaction to prior sargramostim (GM-CSF)
• No hypersensitivity to eggs or egg products
• No active infection within 72 hours of vaccination

Other

• Fertile patients must use effective contraception
• Able to avoid close contact or household contact with the following high-risk individuals for 3 weeks after vaccination:
  • Children under the age of 5
  • Pregnant or nursing women
  • Individuals with prior or concurrent extensive eczema or other eczematoid skin disorders
  • Immunocompromised individuals (by disease or therapy) such as those with AIDS
• No uncontrolled clinically significant serious disease or organ system disorder
• No prior or concurrent extensive eczema
• No other acute, chronic, or exfoliative skin disorder, such as the following:
  • Extensive psoriasis
  • Burns
  • Impetigo
  • Disseminated zoster
  • Varicella zoster
  • Severe acne
  • Open rashes or wounds
• No other malignancy within the past 2 years

Expected Enrollment

A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study.

Outcomes

Progression-free survival

Safety as measured by adverse events
Time to progression
Time to onset tumor-associated pain
Effect of vaccination on PSA levels

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to bisphosphonate use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive vaccinia-PSA-TRICOM vaccine subcutaneously (SC) on day 0 and fowlpox-PSA-TRICOM vaccine SC on days 14, 28, 56, 84, 112, and 140. Sargramostim (GM-CSF) is administered SC on days 0-3, 14-17, 28-31, 56-59, 84-87, 112-115, and 140-143.



• Arm II (control): Patients receive empty vector SC on days 0, 14, 28, 56, 84, 112, and 140 and placebo SC on days 0-3, 14-17, 28-31, 56-59, 84-87, 112-115, and 140-143.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients in the control arm who have disease progression may receive vaccine and GM-CSF on an open-label extension of the study.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Fairooz Kabbinavar, MD, Principal investigator		Ph: 310-206-3921; 888-798-0719

Registry Information
Official Title		A Phase II Randomized, Double Blind, Controlled Study to Evaluate the Safety and Efficacy of PROSTVAC® -VF/TRICOM™ in Combination with GM-CSF in Patients with Androgen-Independent Adenocarcinoma of the Prostate
Trial Start Date		2003-12-04
Registered in ClinicalTrials.gov		NCT00078585
Date Submitted to PDQ		2004-02-23
Information Last Verified		2006-04-11
NCI Grant/Contract Number		CA16042

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