Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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|ClinicalTrials.gov Identifier: NCT01606241|
Recruitment Status : Completed
First Posted : May 25, 2012
Last Update Posted : September 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Breast Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Stage IIA Breast Cancer Stage IIA Fallopian Tube Cancer Stage IIA Ovarian Cancer Stage IIB Breast Cancer Stage IIB Fallopian Tube Cancer Stage IIB Ovarian Cancer Stage IIC Fallopian Tube Cancer Stage IIC Ovarian Cancer Stage IIIA Breast Cancer Stage IIIA Fallopian Tube Cancer Stage IIIA Ovarian Cancer Stage IIIA Primary Peritoneal Cancer Stage IIIB Breast Cancer Stage IIIB Fallopian Tube Cancer Stage IIIB Ovarian Cancer Stage IIIB Primary Peritoneal Cancer Stage IIIC Breast Cancer Stage IIIC Fallopian Tube Cancer Stage IIIC Ovarian Cancer Stage IIIC Primary Peritoneal Cancer Stage IV Fallopian Tube Cancer Stage IV Ovarian Cancer Stage IV Primary Peritoneal Cancer||Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine||Phase 1|
I. To assess the safety of administering one cycle of cyclophosphamide and six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor (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.
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.
III. To determine whether cyclophosphamide treatment, prior to vaccination, results in regulatory T cell depletion by assessing regulatory T cells before and immediately after cyclophosphamide treatment.
IV. To compare FR-alpha (FRa) expression levels in tumor removed at primary surgery to FRa expression levels in tumor removed for clinical purposes at disease recurrence. (For ovarian cancer patients whose disease recurs.)
Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of course 1. Within 3-5 days, 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||July 24, 2012|
|Actual Primary Completion Date :||September 25, 2014|
|Actual Study Completion Date :||March 3, 2018|
Experimental: Treatment (cyclophosphamide and vaccine therapy)
Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine ID on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine
Other Name: FR Alpha Peptide Vaccine
- Proportion of patients who experience severe toxicities (grades 3-5 of the National Cancer Institute's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0) [ Time Frame: Up to 12 months ]Defined as adverse events that are classified as either unrelated, unlikely to be related, possibly, probably, or definitely related to study treatment. 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.
- Disease-free survival [ Time Frame: Time from registration to documentation of disease recurrence, second primary, or death without disease recurrence or second primary, assessed up to 12 months ]The distribution of disease-free survival will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).
- FRa expression [ Time Frame: Up to 12 months ]A 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FRa positive disease. Similarly, a 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FRa negative disease.
- Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 12 months ]The distribution of overall survival times will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).
- Percentage change in plasma concentration of cytokines and chemokines [ Time Frame: Baseline to up to 12 months ]The percent change in plasma concentrations of cytokines and chemokines from pre-treatment concentrations will be determined. Will be plotted against time with the points belonging to a particular individual connected. Each graph will be visually inspected for trends across time and difference between treatment regimens.
- FR-alpha -specific antibody response by enzyme linked immunosorbent assay [ Time Frame: Up to 12 months ]A vaccine-induced FR-alpha-specific antibody responses will be defined as (1) a 2-fold or greater increase in FR-alpha-specific antibody concentration from pretreatment levels at any point during treatment or (2) FR-alpha-specific antibodies above the lower limit of detection at any point during treatment if pre-treatment levels were non-detectable.
- FR-alpha-specific antibody response by enzyme-linked immunospot [ Time Frame: Up to 12 months ]A patient is said to have an antigen-specific response at a given post-treatment time point if one of the following sets of conditions is true: 1) the average antigen specific value at pre-treatment > 0, there is a 2 fold increase in average antigen-specific value at post treatment time relative to antigen specific value at pretreatment, and the post-treatment time point of interest (INT) is wholly above the pre-INT; or (2) the average antigen specific value at pre-treatment =< 0, the average antigen-specific value at post treatment time > 0, and the post-INT is wholly above the pre-INT.
- Percent change in antigen-specific cytokine profiles [ Time Frame: Baseline to up to 12 months ]Percent change in plasma concentrations of cytokines from pre-treatment levels will be examined to determine skewing of the T cell response to type 1 helper cell or type 2 helper cell after vaccination.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01606241
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Matthew Block||Mayo Clinic|