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

NCT03012100 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RU011501INCI-2016-01878P30CA015083
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 12

Brief Summary

This randomized phase II trial studies how well multi-epitope folate receptor alpha peptide vaccine, sargramostim (GM-CSF), and cyclophosphamide work to prevent the recurrence of stage 1-3 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 (GM-CSF), and cyclophosphamide may work well together to prevent cancer recurrence after surgery and other standard treatments for triple negative breast cancer.

Conditions

Bilateral Breast Carcinoma; Breast Inflammatory Carcinoma; 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; Triple-Negative Breast Carcinoma; Unilateral Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  Will be estimated using the method of Kaplan-Meier. Will use the stratified log-rank tests.

  Through study completion (average of 5 years)

Secondary Outcomes (4)

• Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events 4.0

  Through study completion (average of 5 years)

• Overall survival

  Through study completion (average of 5 years)

• Vaccine induced folate receptor [FR]alpha-specific T cell responses defined as the proportion of patients with at least a 2-fold increase in the number of cells/plasma concentration

  Through study completion (average of 5 years)

• FRalpha levels

  Through study completion (average of 5 years)

Study Arms (2)

Arm I (FRalpha peptide vaccine, sargramostim)

EXPERIMENTAL

Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of cycle 1 only. Starting cycle 2, patients receive multi-epitope folate receptor alpha peptide vaccine with sargramostim ID on day 1. Treatment repeats every 28 days for cycles 2-7 and every 6 months for cycles 8-14 in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine; Biological: Sargramostim

Arm II (placebo, sargramostim)

PLACEBO COMPARATOR

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

Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Biological: Sargramostim

Interventions

Cyclophosphamide DRUG

Given PO

Also known as: (-)-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, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm I (FRalpha peptide vaccine, sargramostim); Arm II (placebo, sargramostim)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (FRalpha peptide vaccine, sargramostim); Arm II (placebo, sargramostim)

Multi-epitope Folate Receptor Alpha Peptide Vaccine BIOLOGICAL

Given ID

Also known as: FR Alpha Peptide Vaccine

Arm I (FRalpha peptide vaccine, sargramostim)

Placebo Administration OTHER

Given ID

Arm II (placebo, sargramostim)

Sargramostim BIOLOGICAL

Given ID

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Arm I (FRalpha peptide vaccine, sargramostim); Arm II (placebo, sargramostim)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Female
• Resected unilateral or bilateral primary carcinoma of the breast without clinical evidence of metastatic disease (after neoadjuvant chemotherapy and/or adjuvant chemotherapy), 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 CANCER surgeries, any radiation therapy, and any chemotherapy, whichever is last, \>= 90 days but not \>= 546 days prior to randomization
• Note: Reconstructive and prophylactic surgeries are allowed after randomization (during study treatment)
• Patient had at least one of the following:
• Biopsy or surgery-proven regional node involvement by cancer
• T1c, T2, T3, or T4 disease (with inflammatory disease allowed) identified at the time of surgery or clinically identified prior to neoadjuvant chemotherapy
• No complete response to neoadjuvant chemotherapy (those who did achieve complete response are still eligible if a pre-chemotherapy regional nodal biopsy identified cancer or if the pre-chemotherapy tumor measured \> 1 cm)

You may not qualify if:

• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• 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
• 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
• NOTE: Localized fungal or viral infections including of the skin, nails, mouth, and genital area are allowed
• History of other cancer \< 5 years prior to consent (except non-melanoma skin cancer or carcinoma in situ of the uterine cervix) or current receipt of treatment another cancer (e.g., monoclonal antibody, small molecule pathway inhibitor)
• Treatment with systemic corticosteroid or immune-modulators =\< 7 days prior to randomization
• Concurrent treatment with other experimental drugs or any other systemic anticancer therapy (due to unknown drug-vaccine potential interactions). Use of experimental or other targeted therapy \> 3 months prior is allowed as long as it is not Her2-directed
• 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 or other Her2-directed therapy

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Carle Cancer Center NCI Community Oncology Research Program

Urbana, Illinois, 61801, United States

Location

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Unilateral Breast Neoplasms

Interventions

Cyclophosphamide; sargramostim; Colony-Stimulating Factors

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; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Kathryn J Ruddy

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2016
• First Posted: January 6, 2017
• Study Start: March 31, 2017
• Primary Completion: August 30, 2022
• Study Completion (Estimated): July 31, 2026
• Last Updated: January 13, 2023

Record last verified: 2022-12

Locations

US (12)