A Phase I Trial of the Safety and Immunogenicity of a Multi-epitope Folate Receptor Alpha Peptide Vaccine Used in Combination With Cyclophosphamide in Subjects Previously Treated for Breast or Ovarian Cancer


Rochester, Minn.

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES: I. To assess the safety of administering a course of cyclophosphamide treatment followed by six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor 1 (FR)-alpha (multi-epitope folate receptor alpha peptide vaccine). II. To assess the ability of this vaccination protocol to elicit an immune response as measured by activated FR-alpha-specific T lymphocytes or high-affinity antibodies. CORRELATIVE OBJECTIVES: I. To determine FR-alpha expression status of primary tumors when available as formalin-fixed, paraffin-embedded material and whether expression correlates with the ability to generate an immune response. II. To identify human lymphocyte antigen (HLA) class I binding peptides from FR-alpha that are recognized by lymphocytes from patients prior to and after vaccination. OUTLINE: Patients receive 100 mg cyclophosphamide orally daily for 1 week followed by a 1 week rest, and then another week of cyclophosphamide. Approximately 7-10 days after the last dose of cyclophosphamide, patients receive multi-epitope folate receptor alpha peptide vaccine intradermally (ID) on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3, 6, and 12 months.

Who is eligible to participate?

Inclusion Criteria: - Clinically confirmed no evidence of disease at least 90 days from completion of systemic therapy with the exception of hormonal therapy and bisphosphonates (per practice guidelines for breast and ovarian cancer) - Histological or cytological confirmation of stage II or III breast cancer or stage II, III or IV ovarian/primary peritoneal/fallopian tube cancer. - Note: Patients with stage IV ovarian/primary peritoneal/fallopian tube cancer must register within one year of completing chemotherapy. - Completed systemic treatment (chemotherapy, immune modulators [such as trastuzumab], radiation, and/or corticosteroids) with the exception of hormonal therapy and bisphosphonates at least 90 days prior to registration - Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 0 or 1 - Absolute neutrophil count (ANC) >= 1500/mm^3 - Platelets >= 100,000/ul - Hemoglobin >= 10.0 g/dL - Creatinine =< 1.5 x upper limit of normal (ULN) or 24 hour urine =< grade 2 - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x ULN - Serum albumin >= 3 g/dL - Urinalysis with =< 2+ proteinuria - Thyroid-stimulating hormone (TSH) - negative or =< normal institutional range - Anti-nuclear antibody (ANA) - negative or =< normal institutional range - Serum rheumatoid factor (RF) - negative or =< normal institutional range - Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only - Capable of understanding the investigative nature, potential risks, and benefits of the study and capable of providing valid informed consent - Willing to return to Mayo Clinic Rochester for follow-ups (immunizations, blood draws, etc.) - Willing to provide mandatory blood samples for primary and correlative goals - Willing to receive a tetanus vaccination if you have not had one within the past year Exclusion Criteria: - Any of the following: - Pregnant women - Nursing women unwilling to stop breast feeding - Men or women of childbearing potential who are unwilling to employ adequate contraception from the time of registration through cycle 6 (or the final vaccine cycle for each patient) - Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens - Immunocompromised patients (other than that related to the use of corticosteroids) including patients known to be human immunodeficiency virus (HIV) positive - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Receiving any other investigational agent - Other active malignancy =< 5 years prior to registration; EXCEPTIONS: - Non-melanoma skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (cytotoxics, monoclonal antibodies, small molecule inhibitors) for this cancer - Known history of autoimmune disease - Any contraindication to receiving sargramostim (GM-CSF) or cyclophosphamide - Uncontrolled acute or chronic medical conditions including, but not limited to the following: - Active infection requiring antibiotics - Congestive heart failure (New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease) - Myocardial infarction or stroke within previous 6 months - Use of a systemic steroid =< 30 days prior to registration - Receiving thyroid replacement therapy

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