Brief Title
Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
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
Brief Summary
This phase I clinical trial studies the side effects of vaccine therapy and cyclophosphamide
in treating patients with stage II-III breast cancer or stage II-IV ovarian, primary
peritoneal or fallopian tube cancer. Vaccines made from peptides 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 vaccine
therapy and cyclophosphamide may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES:
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.
SECONDARY 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.
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.)
OUTLINE:
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
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)
Secondary Outcome
Disease-free survival
Condition
Recurrent Breast Carcinoma
Intervention
Cyclophosphamide
Study Arms / Comparison Groups
Treatment (cyclophosphamide and vaccine therapy)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
24
Start Date
July 24, 2012
Completion Date
March 3, 2018
Primary Completion Date
September 25, 2014
Eligibility Criteria
Inclusion Criteria:
- Clinically confirmed no evidence of disease >= 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 >= 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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Matthew Block, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01606241
Organization ID
MC1015
Secondary IDs
NCI-2012-00586
Responsible Party
Sponsor
Study Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Matthew Block, Principal Investigator, Mayo Clinic
Verification Date
September 2018