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).
Brief Title
Folate Receptor Alpha Peptide Vaccine With GM-CSF in Patients With Triple Negative Breast Cancer
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Breast Cancer
Eligibility 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).
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).
Inclusion 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.
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.
Gender
Female
Gender Based
false
Keywords
TNBC
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02593227
Org Class
Industry
Org Full Name
Marker Therapeutics, Inc.
Org Study Id
FRV-002
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Emergence of B and T cell immunity targeting the folate receptor alpha
Outcome Measure
Immune response
Outcome Time Frame
3 years
Secondary Outcomes
Outcome Description
To determine FRα expression status of primary tumors
Outcome Time Frame
Baseline
Outcome Measure
Folate receptor alpha expression
Outcome Description
RFS in relation to FR specific immune response
Outcome Time Frame
3 years
Outcome Measure
Relapse Free Survival
Outcome Description
Incidence of treatment emergent adverse events and injection site reactions
Outcome Time Frame
3 years
Outcome Measure
Safety and tolerability (treatment emergent adverse events and injection site reactions)
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sun Young Oh
Investigator Email
suyoung@montefiore.org
Investigator Phone
918-405-8404