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

NCT02593227 | Completed Phase 2 DMC

• 1 other identifier: FRV-002
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 11

Brief Summary

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).

Conditions

Breast Cancer

Keywords

TNBC

Outcome Measures

Primary Outcomes (1)

• Immune response

  Emergence of B and T cell immunity targeting the folate receptor alpha

  3 years

Secondary Outcomes (3)

• Folate receptor alpha expression

  Baseline

• Relapse Free Survival

  3 years

• Safety and tolerability (treatment emergent adverse events and injection site reactions)

  3 years

Study Arms (4)

Low dose FRα vaccine

EXPERIMENTAL

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

High dose FRα vaccine

EXPERIMENTAL

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

Low dose FRα vaccine + cyclophosphamide

EXPERIMENTAL

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; Drug: Cyclophosphamide

High dose FRα vaccine + cyclophosphamide

EXPERIMENTAL

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; Biological: High dose FRα vaccine

Interventions

Low dose FRα vaccine BIOLOGICAL

165ug per peptide ID injection

Also known as: TPIV200

Low dose FRα vaccine; Low dose FRα vaccine + cyclophosphamide

Cyclophosphamide DRUG

IV infusion over 1 hour

Also known as: Cytoxan

High dose FRα vaccine + cyclophosphamide; Low dose FRα vaccine + cyclophosphamide

High dose FRα vaccine BIOLOGICAL

500ug per peptide ID injection

Also known as: TPIV200

High dose FRα vaccine; High dose FRα vaccine + cyclophosphamide

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patient, age 18 years or older;
• Completely resected unilateral or bilateral primary carcinoma of the breast
• Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures;
• 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.
• Completed primary treatment (surgery and radio/chemotherapy in adjuvant and/or neo-adjuvant setting) \<360 days prior to first vaccination.
• Completed last cycle of chemotherapy or radiation \> 60 days prior to first vaccination
• 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
• Karnofsky index \>= 70%;
• Life expectancy of at least 5 years, disregarding the diagnosis of cancer;
• 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

You may not qualify if:

• Clinical evidence of distant metastases per practice guidelines for breast cancer;
• Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion;
• Known hypersensitivity reaction to the GM-CSF adjuvant; Any known contra-indication to GM-CSF or Cyclophosphamide treatment;
• 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;
• 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);
• 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;
• 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);
• Completed treatment with systemic corticosteroid or immune-modulators \< 30 days prior to registration;
• Planned treatment with other experimental drugs or any other non-hormonal anti-cancer therapy;
• Immunocompromised patients, including patients with known HIV infection;
• Symptomatic thyroid disease, unless negative for thyroid antibodies (TSH receptor, TPO, thyroglobulin).

Sponsors & Collaborators

• Marker Therapeutics, Inc.: lead

Study Sites (11)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Maryland - Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

MidAmerica Division,Inc

Kansas City, Missouri, 64132, United States

Location

The Valley Hospital

Paramus, New Jersey, 07652, United States

Location

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Montefiore Medical Center, Einstein Cancer Center

New York, New York, 10461, United States

Location

Oncology Hematology Care

Cincinnati, Ohio, 45242, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology Presbyterian Cancer Center Dallas

Dallas, Texas, 75231, United States

Location

Related Links

• Corporate website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Richard Kenney, MD

  Marker Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: November 2, 2015
• Study Start: April 1, 2016
• Primary Completion: July 15, 2021
• Study Completion: July 15, 2021
• Last Updated: July 19, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)