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Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02593227
First Posted: November 2, 2015
Last Update Posted: November 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Tapimmune Inc.
  Purpose
This Phase II trial evaluates the safety and immunogenicity of two doses of the Folate Receptor Alpha (FRα) peptide vaccine mixed with GM-CSF as a vaccine adjuvant, with or without a immune priming with cyclophosphamide, as a consolidation therapy after neoadjuvant or adjuvant treatment of patients with Stage IIb-III triple negative breast cancer (TNBC).

Condition Intervention Phase
Breast Cancer Biological: Low dose FRα vaccine Drug: Cyclophosphamide Biological: High dose FRα vaccine Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Multicenter Phase II Trial to Evaluate the Safety and Immunogenicity of Two Doses of Vaccination With Folate Receptor Alpha Peptides With GM-CSF in Patients With Triple Negative Breast Cancer Defined as Primary Tumor That is Her2-neu and Low (< 10%) ER/PR Nuclear Staining

Resource links provided by NLM:


Further study details as provided by Tapimmune Inc.:

Primary Outcome Measures:
  • Immune response [ Time Frame: 3 years ]
    Emergence of B and T cell immunity targeting the folate receptor alpha


Secondary Outcome Measures:
  • Folate receptor alpha expression [ Time Frame: Baseline ]
    To determine FRα expression status of primary tumors

  • Relapse Free Survival [ Time Frame: 3 years ]
    RFS in relation to FR specific immune response

  • Safety and tolerability (treatment emergent adverse events and injection site reactions) [ Time Frame: 3 years ]
    Incidence of treatment emergent adverse events and injection site reactions


Enrollment: 80
Actual Study Start Date: April 2016
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low dose FRα vaccine
FRα peptide vaccine with GM-CSF adjuvant - single ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
Biological: Low dose FRα vaccine
165ug per peptide ID injection
Other Name: TPIV200
Experimental: High dose FRα vaccine
FRα peptide vaccine with GM-CSF adjuvant - triple ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
Biological: High dose FRα vaccine
500ug per peptide ID injection
Other Name: TPIV200
Experimental: Low dose FRα vaccine + cyclophosphamide
Cyclophosphamide 300 mg/sqm as a 1 hour IV infusion 3 days prior to first vaccination. Followed by FRα peptide vaccine with GM-CSF adjuvant - ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
Biological: Low dose FRα vaccine
165ug per peptide ID injection
Other Name: TPIV200
Drug: Cyclophosphamide
IV infusion over 1 hour
Other Name: Cytoxan
Experimental: High dose FRα vaccine + cyclophosphamide
Cyclophosphamide 300 mg/sqm as a 1 hour IV infusion 3 days prior to first vaccination. Followed by FRα peptide vaccine with GM-CSF adjuvant - ID administration - monthly vaccinations repeated 6 times followed by boosters every 6 months until recurrence
Drug: Cyclophosphamide
IV infusion over 1 hour
Other Name: Cytoxan
Biological: High dose FRα vaccine
500ug per peptide ID injection
Other Name: TPIV200

Detailed Description:

Triple negative breast cancers (TNBCs) occur in approximately 20-25% of all patients with breast cancer and are associated with a poor prognosis. Patients with TNBCs derive no benefit from targeted therapies. Excluding those patients who demonstrate a pathologic complete response following neoadjuvant chemotherapy, which is a minor fraction (i.e. 15%), overall survival is only 45% at 7 years.

Following standard of care, there are windows of opportunity to further and safely treat patients to prevent recurrence. Stimulating the immune system to produce T cells immunity specific for tumor antigens may significantly delay recurrence and cure patients.

The proposed vaccine is intended to induce T cells to survey for the reemergence of TNBCs and to prevent recurrence in the adjuvant setting. The vaccine strategy is antigen-specific and targets the Folate Receptor Alpha (FRα). FRα is an ideal target because of its limited expression in the healthy tissues and it high expression in 86% of TNBCs. Studies have shown that it is a biologically important marker that is associated with poorer clinical outcome and is retained in metastatic lesions.

The FRα vaccine include a pool of 5 peptides that are immunogenic epitopes and safely generate tissue-surveying CD4 T cell immune responses in patients tested in a recently completed phase I clinical trial.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female patient, age 18 years or older;
  2. Completely resected unilateral or bilateral primary carcinoma of the breast
  3. Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures;
  4. Primary tumor was negative for ER, PR (cut-off for positivity is >10% positive tumor cells with nuclear staining) and negative for Her2-neu (0 or 1+ on immunohistochemistry and/or normal gene copy number by in-situ hybridization); Central review is not required.
  5. Completed primary treatment (surgery and radio/chemotherapy in adjuvant and/or neo-adjuvant setting) <360 days prior to first vaccination.
  6. Completed last cycle of chemotherapy or radiation > 60 days prior to first vaccination
  7. Either clinical or pathological Stage I (T1c), II, or III according to AJCC 7th edition

    • Note that patients with (i) non-invasive breast cancer (DCIS) alone, (ii) incidental (microscopic) nodal cancer without a primary tumor (pN1mi), or (iii) metastatic disease are excluded.
    • Resected tumor: No evidence of gross tumor at the surgical resection margin noted in the final surgery report. No evidence of gross residual adenopathy
  8. Karnofsky index >= 70%;
  9. Life expectancy of at least 5 years, disregarding the diagnosis of cancer;
  10. Adequate Blood, renal and hepatic function, as determined within 28 days from registration:

    • ANC ≥ 1,500 / mm3
    • Platelet ≥ 100,000 / uL
    • Hgb > 9 g/dL
    • Creatinine ≤ 1.5 x ULN or 24-hour urine < Grade 2
    • Urinalysis with < 2+ proteinuria
    • Serum albumin ≥ 3 g/dL
    • SGOT (AST) ≤ 3 x ULN
  11. Anti-nuclear antibody (ANA) negative or low-positive institutional range, as determined within 28 days from registration. Intermediate values (usually defined by a titer of ≤1:80, or as indicated by institutional range) are acceptable if there are, in the opinion of the Investigator, no early signs of an autoimmune disease.
  12. Primary tumor is available for shipment to central laboratory for analysis of FRα expression by IHC.
  13. Patients must be, in the opinion of the Investigator, available and compliant for treatment and follow-up.

Exclusion Criteria:

  1. Clinical evidence of distant metastases per practice guidelines for breast cancer;
  2. Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion;
  3. Known hypersensitivity reaction to the GM-CSF adjuvant; Any known contra-indication to GM-CSF or Cyclophosphamide treatment;
  4. Pregnant or lactating patients. Patients of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to registration and must implement adequate contraceptive measures during study treatment;
  5. Active autoimmune disease requiring therapy within the past 2 years (Note: patients with vitiligo, Grave's disease or psoriasis not requiring systemic treatment within the past 2 years are not excluded);
  6. Other uncontrolled illness or medical condition, such as active infection, symptomatic heart failure (New York Heart Association class III or IV; moderate to severe objective evidence of cardiovascular disease), unstable angina pectoris, myocardial infarction or stroke within last 6 months, psychiatric illness that may limit compliance with study requirement or interfere with the understanding and giving of informed consent;
  7. Prior active secondary malignancy < 5 years prior to consent (except non-melanomatous skin cancer or carcinoma in situ of the uterine cervix) or currently receiving other specific treatment for this cancer (including monoclonal antibody or pathway inhibitor);
  8. Completed treatment with systemic corticosteroid or immune-modulators < 30 days prior to registration;
  9. Planned treatment with other experimental drugs or any other non-hormonal anti-cancer therapy;
  10. Immunocompromised patients, including patients with known HIV infection;
  11. Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor, TPO, thyroglobulin).
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02593227


Locations
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Kansas
University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
United States, Maryland
University of Maryland - Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Michigan
Karmanos Cancer Center
Detroit, Michigan, United States, 48201
United States, Missouri
MidAmerica Division,Inc
Kansas City, Missouri, United States, 64132
United States, New Jersey
The Valley Hospital
Paramus, New Jersey, United States, 07652
United States, New York
Mount Sinai Hospital
New York, New York, United States, 10029
Montefiore Medical Center, Einstein Cancer Center
New York, New York, United States, 10461
United States, Ohio
Oncology Hematology Care
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology Presbyterian Cancer Center Dallas
Dallas, Texas, United States, 75231
Sponsors and Collaborators
Tapimmune Inc.
Investigators
Study Director: Richard Kenney, MD Tapimmune Inc.
  More Information

Additional Information:
Responsible Party: Tapimmune Inc.
ClinicalTrials.gov Identifier: NCT02593227     History of Changes
Other Study ID Numbers: FRV-002
First Submitted: October 27, 2015
First Posted: November 2, 2015
Last Update Posted: November 16, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Tapimmune Inc.:
TNBC

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vaccines
Cyclophosphamide
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists