Vaccine Plus Montanide ISA-51 and Sargramostim in Treating Patients With Stage IV Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Giving a vaccine with Montanide ISA-51 and sargramostim may cause a stronger immune response and kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy when given together with Montanide ISA-51 and sargramostim in treating patients with stage IV breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the safety of telomerase: 540-548 peptide vaccine emulsified in Montanide ISA-51 and sargramostim (GM-CSF) in patients with HLA-A2-expressing stage IV breast cancer. Secondary Compare the generation of human telomerase reverse transcriptase (hTERT) peptide-specific vs cytomegalovirus peptide-specific cytotoxic T-lymphocyte (CTL) immunity in patients treated with this regimen. Correlate the dose level of this regimen with the generation of hTERT-specific CTL immunity and the development of hTERT-specific autoimmunity in these patients. Determine the tumor response in patients treated with this regimen. OUTLINE: This is a dose-escalation study of the telomerase: 540-548 peptide and CMV 495 peptide portions of the vaccine. Patients receive telomerase: 540-548 peptide and CMV 495 peptide (as an immunological control) vaccine emulsified in Montanide ISA-51 subcutaneously (SC) followed by sargramostim (GM-CSF) SC on day 1 of weeks 1, 3, 5, 7, 11, 15, 19, and 27 (for a total of 8 vaccinations). Treatment continues in the absence of disease progression or unacceptable toxicity. Cohorts of 5-8 patients receive escalating doses of telomerase: 540-548 peptide and CMV 495 peptide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 8 patients experience dose-limiting toxicity. A total of 12 patients receive treatment at the MTD. Patients are followed within 30 days and then at 6 and 12 months. PROJECTED ACCRUAL: A total of 5-28 patients will be accrued for this study.

Official Title
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Phase I Study Of Telomerase Peptide Vaccination For Patients With Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: incomplete Freund's adjuvant
* Biological: sargramostim
* Biological: telomerase: 540-548 peptide vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage IV breast cancer Failed at least 1 prior conventional therapy for metastatic disease Measurable or evaluable disease by clinical, radiographic, or laboratory assessment Measurable lesions must be at least 1 dimension At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are not considered measurable: Pleural effusion Bone lesions Tumor markers HLA-A2-expressing disease by human leukocyte antigen typing No CNS metastases by contrast CT scan and/or MRI No brain metastases within the past 4 years Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 and over Sex Not specified Menopausal status Not specified Performance status ECOG 0-1 Life expectancy More than 6 months Hematopoietic WBC ≥ 3,000/mm^3 Platelet count ≥ 75,000/mm^3 Hemoglobin ≥ 10 g/dL Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT and AST ≤ 2.5 times ULN Hepatitis B negative Hepatitis C negative Renal Creatinine ≤ 1.5 times ULN Immunologic HIV negative Human T-cell lymphotrophic virus-1 negative No active infection No major autoimmune disorder that would preclude study participation Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study participation No alcohol abuse or illicit drug use within the past 12 months No clinically significant comorbid disease or other underlying condition that would preclude study participation No significant psychiatric disorder that would preclude giving informed consent or complying with study PRIOR CONCURRENT THERAPY: Biologic therapy No prior allogeneic or autologous bone marrow or stem cell transplantation More than 30 days since prior hematopoietic growth factors More than 30 days since initiation of prior immunotherapy (e.g., trastuzumab [Herceptin]) Concurrent immunotherapy (e.g., trastuzumab) allowed provided regimen was initiated more than 30 days before study entry, disease is stable or progressive, and patient plans to continue immunotherapy for the duration of study participation No other concurrent hematopoietic growth factors Chemotherapy More than 30 days since prior chemotherapy No concurrent chemotherapy Endocrine therapy More than 30 days since prior glucocorticoids More than 30 days since initiation of prior hormonal therapy (e.g., tamoxifen, anastrozole, or letrozole) Concurrent hormonal therapy (e.g., tamoxifen, anastrozole, or letrozole) allowed provided regimen was initiated more than 30 days before study entry, disease is stable or progressive, and patient plans to continue hormonal therapy for the duration of study participation No concurrent glucocorticoids Radiotherapy More than 30 days since prior radiotherapy No concurrent radiotherapy Surgery Not specified Other More than 14 days since prior anticoagulants (e.g., warfarin, heparin, or enoxaparin) Low-dose anticoagulants to maintain IV catheter patency allowed More than 30 days since prior immunosuppressive drugs More than 30 days since prior experimental therapy No concurrent immunosuppressive drugs No other concurrent investigational products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: incomplete Freund's adjuvant|nan|
|Biological: sargramostim|nan|
|Biological: telomerase: 540-548 peptide vaccine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IV breast cancer