Vaccine Therapy in Treating Patients With Stage III or Stage IV Breast Cancer

Evaluation of the Safety and Immunogenicity of Vaccination With Multiple Synthetic Peptides in Participants With Advanced Breast Cancer

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. Giving booster vaccinations may make a stronger immune response and kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of vaccine therapy in treating patients with stage III or stage IV breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: synthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine

Detailed Description

OBJECTIVES:

Primary

• Determine the safety of a vaccine comprising multiple synthetic breast cancer-associated peptides and a tetanus toxoid helper peptide emulsified in Montanide ISA-51 in patients with stage III or IV adenocarcinoma of the breast.
• Determine, preliminarily, the frequency of immune responses against the 9 class I MHC-restricted peptides in patients treated with the vaccine.
• Determine, preliminarily, the cytotoxic responses of T-cells to allogeneic breast cancer cells and autologous breast cancer cells (when available).

OUTLINE: This is an open-label study.

Patients receive peptide vaccine comprising 9 synthetic breast cancer peptides and tetanus toxoid helper peptide emulsified in Montanide ISA-51 subcutaneously and intradermally once daily on days 1, 8, 15, 36, 57, and 78 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the breast

  • Stage III or IV disease
  • Primary or recurrent disease
  • Invasive lobular carcinoma allowed
• HLA-A1, -A2, -A3, or -A31 positive

• Underwent and recovered from prior primary therapy

  • Patients with no clinical or radiological evidence of disease who had a previous diagnosis of stage III or IV breast cancer must have undergone prior antineoplastic therapy including, but not limited to, surgery, chemotherapy, and radiotherapy within the past 36 months
• Must have at least one undissected axillary and/or inguinal lymph node basin
• No history of brain metastases

• Hormone receptor status

  • Estrogen receptor-positive or -negative tumor

PATIENT CHARACTERISTICS:

• ECOG performance status of 0 or 1
• Body weight > 110 lbs (without clothes)
• Male or female
• Menopausal status not specified
• Absolute neutrophil count > 1000/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 9 g/dL
• Hemoglobin A1c < 7%
• AST and ALT ≤ 2.5 x upper limit of normal (ULN)
• Bilirubin ≤ 2.5 x ULN
• Alkaline phosphatase ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN
• HIV negative
• Hepatitis C negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known or suspected allergies to any component of the vaccine
• No active infection requiring antibiotics
• No New York Heart Association class III or IV heart disease

• No autoimmune disorders requiring cytotoxic or immunosuppressive therapy or autoimmune disorders with visceral involvement, except the following:

  • Laboratory evidence of autoimmune disease (e.g., positive ANA titer) without symptoms
  • Clinical evidence of vitiligo
  • Other forms of depigmenting illness
  • Mild arthritis requiring nonsteroidal antiinflammatory drugs
• No medical contraindication or potential problem that would preclude study participation

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior surgery
• More than 4 weeks since prior and no concurrent chemotherapy and radiotherapy
• More than 4 weeks since prior and no concurrent allergy desensitization injections

• More than 4 weeks since prior parenteral, oral, or inhaled corticosteroids

  • No concurrent inhaled steroids (e.g., Advair® or triamcinolone acetonide)
  • Prior or concurrent topical corticosteroids allowed
• More than 4 weeks since prior and no concurrent growth factors (e.g., epoetin alfa, darbepoetin alfa, or pegfilgrastim)
• More than 4 weeks since prior and no concurrent other investigational medication
• More than 4 weeks since prior and no concurrent other agents with putative immunomodulating activity except for non-steroidal anti-inflammatory agents
• Prior and concurrent hormonal therapy (e.g., tamoxifen, raloxifene, toremifene, fulvestrant, letrozole, anastrozole, or exemestane) allowed

• No prior vaccination with any synthetic peptides in this protocol

  • Vaccines for infectious disease (e.g., influenza) allowed, provided they are administered ≥ 2 weeks prior to or ≥ 2 weeks after study vaccine
• Short term therapy for acute conditions not related to breast cancer allowed
• No concurrent illegal drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Stratum 1: Receiving Hormone Therapy; Patients treated with 9 peptide vaccine who received hormone therapy	Biological: synthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine
EXPERIMENTAL: Stratum 2: Not receiving hormone therapy; Patients receiving 9 peptide vaccine who did not receive hormone therapy	Biological: synthetic breast cancer peptides-tetanus toxoid-Montanide ISA-51 vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Participants Who Experienced Dose-limiting Adverse Events	Safety of the 9-peptide mixture if fewer than 33% of patients experience a dose-limiting toxicity	30 days post administration of last vaccine

Secondary Outcome Measures

Outcome Measure	Time Frame
The Number of Participants With T-cell Responses Against the Vaccine as Measured by Elispot Assay After 14 Day in Vitro Sensitization	Days 1-78

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: David R. Brenin, MD, FACS, University of Virginia

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (ACTUAL): June 1, 2007
• Study Completion (ACTUAL): April 1, 2008

Study Registration Dates

• First Submitted: March 15, 2006
• First Submitted That Met QC Criteria: March 15, 2006
• First Posted (ESTIMATE): March 17, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): April 9, 2013
• Last Update Submitted That Met QC Criteria: February 26, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; male breast cancer; stage IIIC breast cancer; invasive lobular breast carcinoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Monatide (IMS 3015)
• Other Study ID Numbers: 11992; UVACC-BREAST-34; UVACC-HIT-032.7; UVACC-PRC-366-05; UVACC-GCRC-DRB001