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Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01606241
First received: May 23, 2012
Last updated: November 20, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Breast Cancer
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Stage II Breast Cancer
Stage IIA Breast Cancer
Stage IIA Fallopian Tube Cancer
Stage IIA Ovarian Epithelial Cancer
Stage IIA Primary Peritoneal Cavity Cancer
Stage IIB Breast Cancer
Stage IIB Fallopian Tube Cancer
Stage IIB Ovarian Epithelial Cancer
Stage IIB Primary Peritoneal Cavity Cancer
Stage IIC Fallopian Tube Cancer
Stage IIC Ovarian Epithelial Cancer
Stage IIC Primary Peritoneal Cavity Cancer
Stage IIIA Breast Cancer
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Epithelial Cancer
Stage IIIA Primary Peritoneal Cavity Cancer
Stage IIIB Breast Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Epithelial Cancer
Stage IIIB Primary Peritoneal Cavity Cancer
Stage IIIC Breast Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Epithelial Cancer
Stage IIIC Primary Peritoneal Cavity Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Epithelial Cancer
Stage IV Primary Peritoneal Cavity Cancer
Drug: cyclophosphamide
Biological: multi-epitope folate receptor alpha peptide vaccine
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.

  • Vaccine-induced immune response defined as a 2-fold or greater increase in FR-alpha-specific T cells or FR-alpha-specific antibodies in patients with detectable levels at baseline [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    A 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FR-alpha 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 FR-alpha negative disease.

  • Vaccine-induced immune response defined as detectable levels in patients with non-detectable levels at baseline [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    A 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FR-alpha 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 FR-alpha negative disease.


Secondary Outcome Measures:
  • Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 12 months ] [ Designated as safety issue: No ]
    The distribution of overall survival times will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).

  • 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 ] [ Designated as safety issue: No ]
    The distribution of disease-free survival 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 ] [ Designated as safety issue: No ]
    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.

  • FRa expression [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: July 2012
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: cyclophosphamide
Given PO
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Biological: multi-epitope folate receptor alpha peptide vaccine
Given ID
Other Names:
  • FR alpha peptide vaccine
  • FRα peptide vaccine
  • HuFR-1
Other: laboratory biomarker analysis
Correlative studies

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606241

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Matthew Block Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01606241     History of Changes
Other Study ID Numbers: MC1015, NCI-2012-00586, 11-000976, MC1015, P30CA015083
Study First Received: May 23, 2012
Last Updated: November 20, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Abdominal Neoplasms
Adnexal Diseases
Breast Diseases
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Peritoneal Diseases
Skin Diseases
Urogenital Neoplasms
Cyclophosphamide
Vitamin B Complex
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Growth Substances

ClinicalTrials.gov processed this record on November 24, 2014