Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT02593227
- Lead Sponsor
- Marker Therapeutics, Inc.
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 80
-
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
- 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
-
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.
-
Primary tumor is available for shipment to central laboratory for analysis of FRα expression by IHC.
-
Patients must be, in the opinion of the Investigator, available and compliant for treatment and follow-up.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low dose FRα vaccine 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 High dose FRα vaccine 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 Low dose FRα vaccine + cyclophosphamide Low dose FRα vaccine 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 Low dose FRα vaccine + cyclophosphamide 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 High dose FRα vaccine + cyclophosphamide 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 High dose FRα vaccine + cyclophosphamide High dose FRα vaccine 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
- Primary Outcome Measures
Name Time Method Immune response 3 years Emergence of B and T cell immunity targeting the folate receptor alpha
- Secondary Outcome Measures
Name Time Method Folate receptor alpha expression Baseline To determine FRα expression status of primary tumors
Relapse Free Survival 3 years RFS in relation to FR specific immune response
Safety and tolerability (treatment emergent adverse events and injection site reactions) 3 years Incidence of treatment emergent adverse events and injection site reactions
Trial Locations
- Locations (11)
Mount Sinai Hospital
🇺🇸New York, New York, United States
The Valley Hospital
🇺🇸Paramus, New Jersey, United States
University of Maryland - Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
MidAmerica Division,Inc
🇺🇸Kansas City, Missouri, United States
Oncology Hematology Care
🇺🇸Cincinnati, Ohio, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Texas Oncology Presbyterian Cancer Center Dallas
🇺🇸Dallas, Texas, United States
Montefiore Medical Center, Einstein Cancer Center
🇺🇸New York, New York, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States