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

  • Interventional
  • Recruiting
  • NCT03012100
Eligibility Details Visit Clinicaltrials.gov

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

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.

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.

Gender
Female

Age Group
18 Years and up

Accepting Healthy Volunteers?
No

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 > 10% 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

             - Note: If biopsy and surgical specimens are discordant from each other with regard to ER, PR, and/or HER2 status, a patient will be allowed to enroll assuming at least one of the specimens meets the above criteria and no endocrine therapy use is planned going forward

         - Completed planned breast surgeries and any radiation therapy >= 60 days prior to randomization

             - Note: Reconstructive and prophylactic surgeries are allowed after randomization (during study treatment)

         - Completed last cycle of chemotherapy (which can be given in the adjuvant and/or neoadjuvant setting) >= 90 days but not >= 365 days prior to randomization

         - Patient had at least one of the following:

             - Pathologic N1-3

             - Pathologic T2, T3 T4

             - Neoadjuvant chemotherapy and did not achieve complete response at time of surgery (those who did achieve complete response are still eligible if a pre-chemotherapy regional nodal biopsy identified cancer)

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

         - Absolute neutrophil count (ANC) >= 1500/mm^3 obtained =< 14 days prior to randomization

         - Platelet count >= 75,000/uL obtained =< 14 days prior to randomization

         - Aspartate transaminase (AST) =< 3 x upper limit of normal (ULN) obtained =< 14 days prior to randomization

         - Creatinine =< 1.5 x ULN obtained =< 14 days prior to randomization

         - Urine dipstick proteinuria < 2+ or urine protein/creatinine (UPC) ratio =< 1.0 obtained =< 14 days prior to randomization; 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: New primary tumors are allowed, both contralaterally and ipsilaterally, but a prior breast cancer must have been more than 5 years beforehand; also, all patients must have either 1) a positron emission tomography (PET)/computed tomography (CT) or 2) a CT of chest, abdomen and pelvis and a bone scan =< 1 year prior to enrollment; 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

         - Known hypersensitivity reaction to GM-CSF

         - Active autoimmune disease that has required systemic treatment =< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization; Note: replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment; patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded; patients with Celiac disease controlled with diet modification are not excluded

         - 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

         - History of other cancer < 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)

             - NOTE: Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), statins, and other medications commonly used to treat nononcologic, non-autoimmune conditions are allowed

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

         - Prior or concurrent use of trastuzumab

         - Prior or concurrent use of a PD-1 or PD-L1 checkpoint inhibitor including pembrolizumab unless the use was >= 3 months prior to randomization

At a Glance

National Government IDNCT03012100

IRB#IRB17-0544

Lead SponsorAcademic and Community Cancer Research United

Lead PhysicianRita Nanda

Collaborator(s)N/A

EligibilityFemale
18 Years and up
Recruiting