Clinical Trials /

Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer

NCT03012100

Description:

This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide vaccine, sargramostim, and cyclophosphamide work in treating patients with triple negative breast cancer. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving multi-epitope folate receptor alpha peptide vaccine, sargramostim, and cyclophosphamide may work better in treating patients with triple negative breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Multi-epitope Folate Receptor Alpha Peptide Vaccine, Sargramostim, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer
  • Official Title: Double Blind, Parallel Groups, Controlled, Randomized Phase II Trial to Evaluate Vaccination With Folate Receptor Alpha Peptide Vaccine With GM-CSF as Vaccine Adjuvant Following Oral Cyclophosphamide Versus GM-CSF/Placebo to Prevent Recurrence in Patients With Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: RU011501I
  • SECONDARY ID: NCI-2016-01878
  • SECONDARY ID: RU011501I
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03012100

Conditions

  • Bilateral Breast Carcinoma
  • Estrogen Receptor Negative
  • HER2/Neu Negative
  • Progesterone Receptor Negative
  • Stage IB Breast Cancer AJCC v7
  • Stage II Breast Cancer AJCC v6 and v7
  • Stage IIA Breast Cancer AJCC v6 and v7
  • Stage IIB Breast Cancer AJCC v6 and v7
  • Stage III Breast Cancer AJCC v7
  • Stage IIIA Breast Cancer AJCC v7
  • Stage IIIB Breast Cancer AJCC v7
  • Stage IIIC Breast Cancer AJCC v7
  • Stage IV Breast Cancer AJCC v6 and v7
  • Triple-Negative Breast Carcinoma
  • Unilateral Breast Carcinoma

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Arm I (FRalpha peptide vaccine, sargramostim)
Multi-epitope Folate Receptor Alpha Peptide VaccineFR Alpha Peptide VaccineArm I (FRalpha peptide vaccine, sargramostim)
Sargramostim23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, SargramostatinArm I (FRalpha peptide vaccine, sargramostim)

Purpose

This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide vaccine, sargramostim, and cyclophosphamide work in treating patients with triple negative breast cancer. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving multi-epitope folate receptor alpha peptide vaccine, sargramostim, and cyclophosphamide may work better in treating patients with triple negative breast cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To show that multi-epitope folate receptor alpha peptide vaccine (folate receptor
      [FR]alpha peptide vaccine) with sargramostim (GM-CSF) adjuvant will prolong the disease-free
      survival (DFS) compared to GM-CSF adjuvant treatment in patients with triple negative breast
      cancer.

      SECONDARY OBJECTIVES:

      I. To compare the safety and tolerability of metronomic cyclophosphamide followed by FRalpha
      peptide vaccine with GM-CSF versus GM-CSF alone.

      TERTIARY OBJECTIVES:

      I. To determine whether high level of antibody and cellular immune response toward the
      FRalpha measured at baseline is a prognostic factor for vaccine immune response and/or cancer
      relapse.

      II. To determine whether the level of tumor expression of FRalpha at baseline is a prognosis
      factor for vaccine immune response and/or cancer relapse.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21
      of course 1 only. Starting course 2, patients receive multi-epitope folate receptor alpha
      peptide vaccine with sargramostim intradermally (ID) on day 1. Treatment repeats every 28
      days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease
      progression or unacceptable toxicity.

      ARM II: Patients receive cyclophosphamide as in Arm I. Starting course 2, patients receive
      placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for courses
      2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (FRalpha peptide vaccine, sargramostim)ExperimentalPatients receive cyclophosphamide PO BID on days 1-7 and 15-21 of course 1 only. Starting course 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable toxicity.
  • Cyclophosphamide
Arm II (placebo, sagramostim)Placebo ComparatorPatients receive cyclophosphamide as in Arm I. Starting course 2, patients receive placebo vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for courses 2-7 and every 6 months for courses 8-14 in the absence of disease progression or unacceptable toxicity.
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          -  Completely resected unilateral or bilateral primary carcinoma of the breast without
             clinical evidence of disease, negative for estrogen receptor (ER) and progesterone
             receptor (PR) (cut-off for positivity is > 1% positive tumor cells with nuclear
             staining), and negative for HER2 as defined by one of the four situations delineated
             below:

               -  HER2 immunohistochemistry (IHC) expression of 0 or 1+ and in-situ hybridization
                  non-amplified

               -  HER2 IHC expression of 0 or 1+ and in-situ hybridization not done

               -  HER2 IHC expression of 2+ and in-situ hybridization non-amplified

               -  IHC not done and in-situ hybridization non-amplified

               -  Note: central review is not required

          -  Completed planned breast surgeries and any radiation therapy >= 30 days prior to
             randomization

          -  Completed last cycle of chemotherapy (which can be given in the adjuvant and/or
             neoadjuvant setting) >= 60 days but not >= 365 days prior to randomization

          -  Patient has at least one of the following:

               -  Pathologic N1-3

               -  Pathologic T3

               -  Neoadjuvant chemotherapy and did not achieve pathologic response at time of
                  surgery

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 75,000/uL

          -  Aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)

          -  Creatinine =< 1.5 x ULN

          -  Urine dipstick proteinuria < 2+ or urine protein/creatinine (UPC) ratio =< 1.0; Note:
             patients discovered to have >= 2+ proteinuria on dipstick urinalysis at baseline
             should undergo a 24-hour urine collection and must demonstrate =< 1 g of protein in 24
             hours

          -  Negative serum pregnancy test done =< 14 days prior to randomization, for women of
             childbearing potential only

          -  Provide informed written consent

          -  Willing to return to enrolling institution for follow-up

          -  Willing to provide tissue and blood samples for correlative research studies

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Clinical evidence of local recurrence or distant metastases; Note: all patients must
             have either a positron emission tomography (PET)/computed tomography (CT) or a CT of
             chest, abdomen and pelvis and a bone scan; if one or more of these is concerning for
             distant metastases, follow-up imaging and/or biopsy should be performed to rule out
             distant metastases prior to randomization

          -  Inflammatory breast cancer or tumor with deep adherence or cutaneous invasion

          -  Known hypersensitivity reaction to GM-CSF

          -  History of auto-immune disease per physician discretion

          -  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

          -  Prior secondary malignancy < 5 years prior to consent (except non-melanoma skin cancer
             or carcinoma in situ of the uterine cervix) or receiving other specific treatment for
             this cancer (monoclonal antibody, small molecule pathway inhibitor)

          -  Treatment with systemic corticosteroid or immune-modulators =< 30 days prior to
             randomization

          -  Concurrent treatment with other experimental drugs or any other systemic anticancer
             therapy (due to unknown drug-vaccine potential interactions)

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy

          -  Prior or concurrent use of trastuzumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Disease-free survival
Time Frame:Through study completion (average of 5 years)
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.

Secondary Outcome Measures

Measure:FRalpha levels
Time Frame:Through study completion (average of 5 years)
Safety Issue:
Description:FR alpha levels at baseline will be examined as a prognostic factor in the vaccine immune response. A multivariable Cox proportional hazard model will be used to assess baseline FR alpha levels as a potential prognostic factor for immune response.
Measure:Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events 4.0
Time Frame:Through study completion (average of 5 years)
Safety Issue:
Description: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. Will use the Cochran-Mantel Haenszel chi-squared test with study stratification factors. Will use logistic regression to test differences in proportions while controlling for the known covariates.
Measure:Overall survival
Time Frame:Through study completion (average of 5 years)
Safety Issue:
Description:Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.
Measure:Vaccine induced FRalpha-specific T cell responses defined as the proportion of patients with at least a 2-fold increase in the number of cells/plasma concentration
Time Frame:Through study completion (average of 5 years)
Safety Issue:
Description:Will be determined along with its corresponding 95% confidence interval.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Academic and Community Cancer Research United

Last Updated

February 6, 2018