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

VADIS Trial: Phase II Trial of Nelipeimut-S Peptide Vaccine in Women With DCIS of the Breast

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.

Study Overview

• Status: Completed
• Conditions: Breast Ductal Carcinoma In Situ
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Surgical Procedure; Biological: Sargramostim; Drug: Nelipepimut-S Plus GM-CSF Vaccine

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate for nelipepimut-S-specific cytotoxic T lymphocyte (CTL; cluster of differentiation [CD]8+ T cell) response in patients receiving NeuVax (nelipepimut-S plus GM-CSF [sargramostim]) compared to patients receiving GM-CSF alone (control).

SECONDARY OBJECTIVES:

I. Toxicity profile and frequency of adverse events in women with ductal carcinoma in situ (DCIS) of the breast receiving nelipepimut-S vaccine as compared to women receiving GM-CSF alone.

II. Presence of DCIS at resection. III. Difference in HER2 expression in the biopsy and the surgical specimen excised post-vaccination.

IV. Histologic responses:

IVa. Degree of lymphocyte infiltration determined on hematoxylin and eosin (H&E) stained slides and immune infiltration as determined by multiplex immunofluorescence staining for markers including but not limited to CD3, CD4 and CD8.

IVb. Immune infiltrates in normal tissue maximally distant from the tumor (in mastectomy samples).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive nelipepimut-S plus GM-CSF vaccine intradermally (ID) on days 0 and 14 and then undergo surgery on day 28.

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

After completion of study treatment, patients are followed up at 1 and 3 months.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10032
      • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• The ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (nelipepimut-S plus GM-CSF vaccine); 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; Correlative studies; Procedure: Surgical Procedure; Undergo surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS; Drug: Nelipepimut-S Plus GM-CSF Vaccine; Given ID; Other Names: 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
Active Comparator: Arm II (sargramostim); Patients receive sargramostim ID on days 0 and 14 and then undergo surgery on day 28.	Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Surgical Procedure; Undergo surgery; Other Names: Operation; Surgery; Surgery Type; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Surgery, NOS; Biological: Sargramostim; Given ID; Other Names: 23-L-Leucinecolony-Stimulating Factor 2; DRG-0012; Leukine; Prokine; rhu GM-CFS; Sagramostim; Sargramostatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-tumoral Tumor-infiltrating Lymphocytes (iTILs) Within the Basement Membrane	Change from baseline in the iTILs at surgical resection. Wilcoxon rank sum test exact P-value was used.	Baseline to surgical resection, up to 5 weeks
Intra-tumoral Tumor-infiltrating Lymphocytes (iTILs)	Change from baseline in the iTILs at surgical resection. Wilcoxon rank sum test exact P-value was used.	Baseline to surgical resection, up to 5 weeks
Number of Participants With HER2 Expression in Biopsy and Resection Specimens	Difference in HER2 Expression in Biopsy and Resection Specimens. Differences were assessed using a Fisher's exact test.	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	The number of serious and non serious adverse events for both arms. 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)	Presence of DCIS with Invasive Cancer.	At resection

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Cell Analysis	Will utilize tissue-based cyclic immunofluorescence (t-CyCIF), a novel, highly multiplexed imaging modality that follows the imaging of formalin-fixed, paraffin embedded (FFPE) tissue sections at subcellular resolution across 20-60 distinct antigen channels. 4-6 panels that will be used include both my not be limited to an already optimized immune panel.	up to 6 months after completion of the vaccination series timepoint
Immune Infiltrates in Normal Tissue Maximally Distant From the Tumor (in Mastectomy Samples)	In the mastectomy samples only will perform core needle biopsies of the normal tissue, maximally distant from the tumor (ex vivo after the mastectomy if performed and store for future studies of immune infiltrates.	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
Degree of Lymphocyte Infiltration	We will define intra-tumoral TIL as those within the basement membrane. Stromal TIL will be defined as those in the periductal/lobular stroma including the intralobular stromal infiltrate. Cells in the interlobular stromal inflammatory infiltrate will be excluded. All mononuclear cells will be scored but polymorphonuclear leukocytes will be excluded. Intra-tumoral and stromal TILs will be scored as a continuous variable and the percentage of in the surgical specimen will be compared to that in the pre-vaccination diagnostic biopsy.	Up to 6 months after completion of the vaccination series timepoint

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Powel H Brown, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2016
• Primary Completion (Actual): July 22, 2019
• Study Completion (Actual): May 17, 2023

Study Registration Dates

• First Submitted: December 18, 2015
• First Submitted That Met QC Criteria: December 18, 2015
• First Posted (Estimated): December 22, 2015

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Breast Neoplasms; Neoplasms, Ductal, Lobular, and Medullary; Breast Carcinoma In Situ; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Ductal, Breast; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Vaccines; Sargramostim; Molgramostim
• Other Study ID Numbers: NCI-2015-02189 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA016672 (U.S. NIH Grant/Contract); N01-CN-2012-00034 (CTRP (Clinical Trial Reporting Program)); N01CN00034 (U.S. NIH Grant/Contract); 2016-0164 (Other Identifier: M D Anderson Cancer Center); MDA2014-04-02 (Other Identifier: DCP)