Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer

NCT02636582 | Completed Phase 2 Results DMC

• 6 other identifiers: NCI-2015-02189N01-CN-2012-000342016-0164MDA2014-04-02N01CN00034P30CA016672
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well nelipepimut-S plus GM-CSF vaccine therapy or sargramostim works in treating patients with breast cancer. Vaccines made from peptide or antigen and/or a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells that express breast cancer antigens. It is not yet known whether nelipepimut-S plus GM-CSF vaccine or sargramostim is more effective in treating patients with breast cancer.

Conditions

Breast Ductal Carcinoma In Situ

Outcome Measures

Primary Outcomes (1)

• Mean Percent of Nelipepimut-S-specific Cytotoxic T Lymphocyte Response (E75)

  Change from baseline in the Mean percent of Nelipepimut-S-specific cytotoxic T lymphocyte response one-month post-surgical resection. Wilcoxon rank sum test exact P-value was used.

  One-Month post-surgical resection from baseline

Secondary Outcomes (5)

• Intra-tumoral Tumor-infiltrating Lymphocytes (iTILs) Within the Basement Membrane

  Baseline to surgical resection, up to 5 weeks

• Intra-tumoral Tumor-infiltrating Lymphocytes (iTILs)

  Baseline to surgical resection, up to 5 weeks

• Number of Participants With HER2 Expression in Biopsy and Resection Specimens

  Baseline to surgical resection, up to 5 weeks

• Number of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03

  3-6 months after surgery

• Number of Participants With Presence of Ductal Carcinoma in Situ (DCIS)

  At resection

Other Outcomes (4)

• Immune Cell Analysis

  up to 6 months after completion of the vaccination series timepoint

• Immune Infiltrates in Normal Tissue Maximally Distant From the Tumor (in Mastectomy Samples)

  Up to 6 months after completion of the vaccination series timepoint

• Toxicity Profile According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03)

  up to 3 months after surgery

Study Arms (2)

Arm I (nelipepimut-S plus GM-CSF vaccine)

EXPERIMENTAL

Patients receive nelipepimut-S plus GM-CSF vaccine ID on days 0 and 14 and then undergo surgery on day 28.

Other: Laboratory Biomarker Analysis; Drug: Nelipepimut-S Plus GM-CSF Vaccine; Procedure: Surgical Procedure

Arm II (sargramostim)

ACTIVE COMPARATOR

Patients receive sargramostim ID on days 0 and 14 and then undergo surgery on day 28.

Other: Laboratory Biomarker Analysis; Biological: Sargramostim; Procedure: Surgical Procedure

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (nelipepimut-S plus GM-CSF vaccine); Arm II (sargramostim)

Nelipepimut-S Plus GM-CSF Vaccine DRUG

Given ID

Also known as: E75 Plus GM-CSF, E75 Vaccine Plus GM-CSF, HLA A2/A3-Restricted HER-2/neu Peptide Vaccine Plus GM-CSF, Nelipepimut-S Plus Sargramostim, NeuVax Plus GM-CSF

Arm I (nelipepimut-S plus GM-CSF vaccine)

Sargramostim BIOLOGICAL

Given ID

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

Arm II (sargramostim)

Surgical Procedure PROCEDURE

Undergo surgery

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Arm I (nelipepimut-S plus GM-CSF vaccine); Arm II (sargramostim)

Eligibility Criteria

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

You may qualify if:

• Participants must be pre- or post-menopausal
• Participants must have a diagnosis of DCIS made by core needle biopsy
• Participants must be human leukocyte antigen (HLA)-A2 positive
• Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 (Karnofsky \>= 60%)
• Clinical chemistry less than 2 x normal upper limit of normal range
• Platelets \>= 100,000/mm\^3
• Hemoglobin \>= 10 g/dL
• Blood urea nitrogen \< 2 x upper limit of normal (ULN)
• Alkaline phosphatase \< 2 x ULN
• Lactate dehydrogenase \< 2 x ULN
• Creatinine \< 2 x ULN
• Bilirubin \< 2 x ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2 x ULN
• A normal ejection fraction, as defined by the participant's institution; only limited echocardiograms (ECHOs) will be used as cardiac evaluation; no other tests are allowed; ECHO is to be done only in HLA-A2 positive participants; if ECHO has been done within 30 days prior to randomization and results showing a normal ejection fraction have been obtained prior to randomization, an additional ECHO is not needed at baseline
• Willingness to comply with all study interventions and follow-up procedures

You may not qualify if:

• Invasive breast cancer; areas of microinvasion or suspicious for microinvasion on the core biopsy is allowed
• History of prior breast cancer treated within the past two years; patients completing all breast cancer-specific treatment over two years prior to the current diagnosis are eligible
• History of prior ductal carcinoma in situ (DCIS) treated within the past two years; patients completing all treatment for a previous diagnosis of DCIS over two years prior to the current diagnosis are eligible
• Prior lobular carcinoma in situ (LCIS) is allowed
• Pregnant, unwilling to use adequate contraception during study treatment duration or breastfeeding; the effects of NeuVax on the developing human fetus are unknown; for this reason and because NeuVax may be teratogenic, pregnant women will be excluded; all heterosexually active women who may become pregnant must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation OR be post-menopausal defined as any one of the following 1) prior hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior chemotherapy or 3) absence of menstrual period for 2 years in women with a prior history of chemotherapy exposure who were pre-menopausal prior to chemotherapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Any autoimmune disease or other medical condition that, in the opinion of the investigator, would compromise the subject's safety
• Immune deficiency diseases such as immunoglobulin deficiency or immunosuppressive therapy that might interfere with appropriate immune response
• Known history of or known active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C
• Patients on chronic steroid therapy or other immunosuppressive therapy except for topical or inhaled steroids known to have low systemic absorption
• Patients with a known hypersensitivity to GM-CSF, yeast-derived products, or any component of the GM-CSF product (e.g., mannitol)
• Concurrent treatment with other investigational agent
• History of non-breast malignancy within 5 years prior to randomization, except curatively treated superficial bladder cancer, carcinoma in situ of the cervix (stage 0-1), and basal cell or squamous cell carcinoma of the skin
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to NeuVax
• 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
• No recent or planned immunotherapy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

HER2 peptide (369-377); Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Colony-Stimulating Factors; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Isabelle Bedrosian, MD, Professor, Breast Surgical Oncology
• Organization: UT MD Anderson Cancer Center

ibedrosian@mdanderson.org

(713) 563-1872

Study Officials

• Powel H Brown

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 22, 2015
• Study Start: June 14, 2016
• Primary Completion: July 22, 2019
• Study Completion: May 17, 2023
• Last Updated: December 5, 2023
• Results First Posted: May 16, 2023

Record last verified: 2023-11

Locations

US (4)