This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide vaccine, sargramostim (GM-CSF), and cyclophosphamide work to prevent the recurrence of stage 1-3 triple negative breast cancer. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving multi-epitope folate receptor alpha peptide vaccine, sargramostim (GM-CSF), and cyclophosphamide may work well together to prevent cancer recurrence after surgery and other standard treatments for triple negative breast cancer.
PRIMARY OBJECTIVE: I. To show that multi-epitope folate receptor alpha peptide vaccine (folate receptor \[FR\]alpha peptide vaccine) with sargramostim (GM-CSF) adjuvant will prolong the disease-free survival (DFS) compared to GM-CSF adjuvant treatment in patients with triple negative breast cancer. SECONDARY OBJECTIVE: I. To compare the safety and tolerability of metronomic cyclophosphamide followed by FRalpha peptide vaccine with GM-CSF versus GM-CSF alone. CORRELATIVE RESEARCH OBJECTIVES: I. To determine whether high level of antibody and cellular immune response toward the FRalpha measured at baseline is a prognostic factor for vaccine immune response and/or cancer relapse. II. To determine whether the level of tumor expression of FRalpha at baseline is a prognosis factor for vaccine immune response and/or cancer relapse. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim intradermally (ID) on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive cyclophosphamide as in Arm I. Starting cycle 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
280
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Carle Cancer Center NCI Community Oncology Research Program
Urbana, Illinois, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
...and 2 more locations
Disease-free survival
Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.
Time frame: Through study completion (average of 5 years)
Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events 4.0
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns. Will use the Cochran-Mantel Haenszel chi-squared test with study stratification factors. Will use logistic regression to test differences in proportions while controlling for the known covariates.
Time frame: Through study completion (average of 5 years)
Overall survival
Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.
Time frame: Through study completion (average of 5 years)
Vaccine induced folate receptor [FR]alpha-specific T cell responses defined as the proportion of patients with at least a 2-fold increase in the number of cells/plasma concentration
Will be determined along with its corresponding 95% confidence interval.
Time frame: Through study completion (average of 5 years)
FRalpha levels
FRalpha levels at baseline will be examined as a prognostic factor in the vaccine immune response. A multivariable Cox proportional hazard model will be used to assess baseline FRalpha levels as a potential prognostic factor for immune response.
Time frame: Through study completion (average of 5 years)
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