Know Cancer

or
forgot password

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


Phase 1
18 Years
N/A
Open (Enrolling)
Female
Recurrent Breast Cancer, Recurrent Fallopian Tube Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Ovarian Germ Cell Tumor, Recurrent Primary Peritoneal Cavity Cancer, Stage IIA Ovarian Epithelial Cancer, Stage IIA Ovarian Germ Cell Tumor, Stage IIA Primary Peritoneal Cavity Cancer, Stage IIB Ovarian Epithelial Cancer, Stage IIB Ovarian Germ Cell Tumor, Stage IIB Primary Peritoneal Cavity Cancer, Stage IIC Ovarian Epithelial Cancer, Stage IIC Ovarian Germ Cell Tumor, Stage IIC Primary Peritoneal Cavity Cancer, Stage IIIA Breast Cancer, Stage IIIA Ovarian Epithelial Cancer, Stage IIIA Ovarian Germ Cell Tumor, Stage IIIA Primary Peritoneal Cavity Cancer, Stage IIIB Breast Cancer, Stage IIIB Ovarian Epithelial Cancer, Stage IIIB Ovarian Germ Cell Tumor, Stage IIIB Primary Peritoneal Cavity Cancer, Stage IIIC Breast Cancer, Stage IIIC Ovarian Epithelial Cancer, Stage IIIC Ovarian Germ Cell Tumor, Stage IIIC Primary Peritoneal Cavity Cancer

Thank you

Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

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)at 12 months.

Outcome Description:

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.

Outcome Time Frame:

Up to 12 months after completion of study treatment

Safety Issue:

Yes

Principal Investigator

Keith Knutson

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

MC1015

NCT ID:

NCT01606241

Start Date:

July 2012

Completion Date:

Related Keywords:

  • Recurrent Breast Cancer
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Ovarian Germ Cell Tumor
  • Recurrent Primary Peritoneal Cavity Cancer
  • Stage IIA Ovarian Epithelial Cancer
  • Stage IIA Ovarian Germ Cell Tumor
  • Stage IIA Primary Peritoneal Cavity Cancer
  • Stage IIB Ovarian Epithelial Cancer
  • Stage IIB Ovarian Germ Cell Tumor
  • Stage IIB Primary Peritoneal Cavity Cancer
  • Stage IIC Ovarian Epithelial Cancer
  • Stage IIC Ovarian Germ Cell Tumor
  • Stage IIC Primary Peritoneal Cavity Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIA Ovarian Epithelial Cancer
  • Stage IIIA Ovarian Germ Cell Tumor
  • Stage IIIA Primary Peritoneal Cavity Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIB Ovarian Epithelial Cancer
  • Stage IIIB Ovarian Germ Cell Tumor
  • Stage IIIB Primary Peritoneal Cavity Cancer
  • Stage IIIC Breast Cancer
  • Stage IIIC Ovarian Epithelial Cancer
  • Stage IIIC Ovarian Germ Cell Tumor
  • Stage IIIC Primary Peritoneal Cavity Cancer
  • Breast Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Germinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial

Name

Location

Mayo Clinic Rochester, Minnesota  55905