Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02636582|
Recruitment Status : Active, not recruiting
First Posted : December 22, 2015
Last Update Posted : January 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Breast Ductal Carcinoma In Situ||Other: Laboratory Biomarker Analysis Drug: Nelipepimut-S Plus GM-CSF Vaccine Biological: Sargramostim Procedure: Surgical Procedure||Phase 2|
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).
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 (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||VADIS Trial: Phase II Trial of Nelipeimut-S Peptide Vaccine in Women With DCIS of the Breast|
|Actual Study Start Date :||June 14, 2016|
|Actual Primary Completion Date :||July 22, 2019|
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
Drug: Nelipepimut-S Plus GM-CSF Vaccine
Procedure: Surgical Procedure
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
Procedure: Surgical Procedure
- Change in the number of nelipepimut-S-cytotoxic T lymphocytes (CTL), detected using a dextramer assay [ Time Frame: Pre-vaccination to up to 1 month after surgery ]Change of nelipepimut-S-specific CTL at the 1 month (+/- 7 days) after completion of the vaccination series timepoint from baseline will be estimated for each group using mean, standard deviation, median, minimum and maximum. Two-sample t-test or Wilcoxon rank sum test, whichever appropriate, will be used to compare the change between the two groups. Nelipepimut-S-specific CTL will also be measured repeatedly through 6 months after the last vaccination. Repeated measures analysis including mixed effects model will be performed to analyze the effect of treatment on nelipepimut-S-specific CTL change over time.
- Toxicity profile according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.03 [ Time Frame: Up to 3 months after surgery ]Compared between the two groups. Adverse events by grade and relationship will be summarized by tabulation for each group.
- Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.03 [ Time Frame: Up to 3 months after surgery ]Adverse events by grade and relationship will be summarized by tabulation for each group.
- Presence of ductal carcinoma in situ (DCIS) [ Time Frame: At resection ]The histologic data will be presented in tabular form to examine whether the vaccine treatment is associated with the absence of DCIS, induction of necrosis, reduction in histologic grade, or a reduction in the size of DCIS. These data will be descriptive only. The data will be obtained from the standard surgical pathology report generated as part of the patient's clinical care. Formal comparisons of these parameters would likely require a larger sample size to see a statistically significant difference in presence of DCIS, induction of necrosis, or reduction in size of DCIS.
- Difference in HER2 expression [ Time Frame: In the biopsy and the surgical specimen excised post-vaccination ]HER2 scoring will be determined according to the American Society of Clinical Oncology/College of American Pathologists clinical guidelines. Positive cases are those with circumferential membrane staining that is complete, intense, and within > 10% of tumor cells (score 3+). Negative cases are defined as those with no observable staining, or membrane staining that is incomplete and is faint/barely perceptible and within less than or equal to 10% of tumor cells (score 0) or incomplete membrane staining that is faint/barely perceptible and within > 10% of tumor cells (score 1+). Equivocal or indeterminate cases are those with circumferential membrane staining that is incomplete and or weak/moderate and within > 10% of tumor cells or complete and circumferential membrane staining that is intense and within less than or equal to 10% of tumor cells (score 2+). Pre-vaccination and post-vaccination specimens will be compared.
- Degree of lymphocyte infiltration [ Time Frame: Up to 6 months after completion of the vaccination series timepoint ]Will define intra-tumoral tumor infiltration lymphocyte (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.
- Immune cell analysis [ Time Frame: Up to 6 months after completion of the vaccination series timepoint ]Will utilize tissue-based cyclic immunofluorescence (t-CyCIF), a novel, highly multiplexed imaging modality that allows for the imaging of formalin-fixed, paraffin embedded (FFPE) tissue sections at subcellular resolution across 20-60 distinct antigen channels. 4-6 Antibody panels that will be used include but may not be limited to an already optimized immune panel.
- Immune infiltrates in normal tissue maximally distant from the tumor (in mastectomy samples) [ Time Frame: Up to 6 months after completion of the vaccination series timepoint ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02636582
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center|
|New York, New York, United States, 10032|
|United States, Pennsylvania|
|Thomas Jefferson University Hospital|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Elizabeth A Mittendorf||M.D. Anderson Cancer Center|