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

Alternate Title

Vaccine Therapy in Treating Patients With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	DFCI-02310 NCI-5747, NCT00071942, 5747

Objectives

Primary

1. Determine the toxicity of vaccination comprising recombinant vaccinia-MUC-1 and recombinant vaccinia-TRICOM vaccine in patients with metastatic breast cancer.
2. Determine the maximum tolerated dose of this regimen in these patients.
3. Determine the toxicity of this regimen when administered with sargramostim (GM-CSF) in these patients.

Secondary

1. Determine the host immune reactivity in patients treated with this regimen with or without GM-CSF.
2. Determine the antitumor activity in patients treated with this regimen with or without GM-CSF.

Entry Criteria

Disease Characteristics:

• Histologically confirmed metastatic breast cancer



• Meets 1 of the following criteria:
  • Tumor tissue stains positive with monoclonal antibodies DF3 and/or DF3-P
  • Elevated CA 15-3



• Received at least 1 prior regimen of chemotherapy, immunotherapy, or hormonal therapy



• HLA status known



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• Prior vaccinia (smallpox) exposure required
• At least 21 days since prior flu vaccination
• No prior vaccinia vectors or MUC1
• No other concurrent anticancer biologic therapy (e.g., interferon or interleukin)

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior hormonal therapy
• No concurrent hormonal treatment
• No concurrent steroid therapy
  • Steroid creams or inhalers allowed
• No concurrent dexamethasone or other steroids for antiemetic purposes

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• No prior splenectomy

Other

• Recovered from all prior therapy
• At least 3 days since prior antibiotics for active infection

Patient Characteristics:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 2,000/mm³
• Platelet count greater than 100,000/mm³

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• SGPT less than 3 times upper limit of normal

Renal

• Creatinine no greater 2.0 mg/dL

Immunologic

• No active or prior extensive eczema or other eczematoid skin disorders
• No active, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open wounds or rashes)
• No clinical evidence of altered immune responsiveness
• No immunodeficiency or immunosuppression by disease or therapy
• No autoimmune syndromes (e.g., scleroderma or systemic lupus erythematosus)
• No prior allergic or untoward reaction to vaccinia (smallpox) vaccination
• No allergy to eggs
• No active infection requiring antibiotics
• HIV negative

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 4 weeks after study participation
• No history of seizures, encephalitis, or multiple sclerosis
• Must be able to avoid close household contact with any of the following individuals for at least 3 weeks after study vaccination:
  • Persons with active or prior extensive eczema or other eczematoid skin disorders
  • Persons with acute, chronic, or exfoliative skin disorders
  • Pregnant or nursing women
  • Children under age 5
  • Immunodeficient or immunosuppressed persons (by disease or therapy, including HIV infection)
• No other concurrent serious medical condition that would preclude study participation

Expected Enrollment

A total of 11-22 patients will be accrued for this study within 18-24 months.

Outline

This is an open-label, dose-escalation study.

Patients receive vaccination comprising recombinant vaccinia-MUC-1 and recombinant vaccinia-TRICOM vaccine intradermally on days 1 and 29 (for a total of 2 doses) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of recombinant vaccinia-MUC-1 and recombinant vaccinia-TRICOM vaccine 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. Once the MTD is determined, an additional 10 patients (including 5 HLA-A2-positive patients) receive vaccination as above at the MTD and sargramostim (GM-CSF) subcutaneously on days 1-4 and 29-32.

Patients are followed at 4 weeks, monthly until disease progression, and then annually for up to 15 years.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Joseph Paul Eder, MD, Principal investigator		Ph: 617-632-5588; 866-790-4500 Email: joseph_eder@dfci.harvard.edu

Registry Information
Official Title		A Phase I Trial of an Admixture of Recombinant Vaccinia Virus that Express DF3/MUC1 and rV-TRICOM (B7.ICAM-1, and LFA-3) in Patients with Metastatic Adenocarcinoma of the Breast
Trial Start Date		2003-10-03
Registered in ClinicalTrials.gov		NCT00071942
Date Submitted to PDQ		2003-09-18
Information Last Verified		2007-01-04
NCI Grant/Contract Number		CA62490, CA06516