This phase II trial studies how well a vaccine, STEMVAC, works in combination with standard endocrine-based therapy (ET) with a CDK4/6 targeted drug therapy, or with the chemotherapy drug capecitabine, in treating patients with hormone receptor (HR)-positive, HER2-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). STEMVAC is designed to target proteins that cancer cells use when they become more aggressive and start to spread, and it is believed to work by boosting the immune system to recognize and destroy the invader tumor cells that are causing the disease. Standard ET is treatment that adds, blocks, or removes hormones in order to slow or stop the growth of cancer. Standard CDK4/6 inhibitors, including abemaciclib, may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Capecitabine is in a class of medications called antimetabolites. It is taken up by tumor cells and breaks down into fluorouracil, a substance that kills tumor cells. Giving STEMVAC in combination with standard ET or chemotherapy may be an effective treatment for metastatic HR positive, HER2 negative breast cancer.
OUTLINE: Patients with ET-sensitive disease are assigned to Cohort 1, while patients with ET-resistant disease are assigned to Cohort 2. COHORT 1: After completion of 2 cycles of standard of care (SOC) ET + CDK4/6 inhibitor (CDK4/6i) therapy or abemaciclib alone, patients receive STEMVAC intradermally (ID) on the following schedule: 1) Three "priming" doses every 28 days; 2) Two "booster" doses at 6 and 9 months after "priming" dose #1; and 3) Additional "booster" doses every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo image-guided biopsies for research purposes, as well as collection of blood samples and computed tomography (CT) or positron emission tomography (PET) scans throughout the trial. COHORT 2: After completion of 1 cycle of SOC capecitabine treatment, patients receive STEMVAC ID on the following schedule: 1) Three "priming" doses every 28 days; 2) Two "booster" doses at 6 and 9 months after "priming" dose #1; and 3) Additional "booster" doses every 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo image-guided biopsies for research purposes, collection of blood samples, and fluoroestradiol (FES) positron emission tomography (PET) scans, as well as CT or PET scans throughout the trial. After completion of study treatment, patients are followed every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Given ID
Given SOC capecitabine
Undergo CT or ultrasound-guided biopsies
Given SOC CDK4/6i
Given SOC CDK4/6i
Undergo FES PET
Given SOC ET
Undergo PET or FES PET
Undergo image-guided biopsies
Undergo collection of blood samples
Given SOC abemaciclib
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
RECRUITINGIncidence of adverse events (AEs)
Safety and systemic toxicity will be determined by chemical and clinical parameters evaluated at various time points. Toxicity grading will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 6.0 and monitoring of AEs will be done per Food and Drug Administration and NCI guidelines. The type and grade of toxicities noted during the immunization regimen will be summarized. The duration of toxicities will also be summarized using descriptive statistics such as mean and standard deviation. All AEs noted by the investigator will be tabulated according to the affected body system. The frequency and severity of adverse events will be summarized with a proportion and a 95% confidence interval (CI).
Time frame: Up to 3 years after completion of study treatment
Incidence of immunogenicity
Will be defined as the sum of the interferon gamma enzyme-linked immunosorbent spot of all STEMVAC antigens on blood samples collected pre-vaccine as compared to 1-month post dose #3 of the STEMVAC vaccine and again after 2 booster doses of STEMVAC vaccine. Both incidence and magnitude will be assessed. Immune responses will be summarized with mean and standard deviation or median and range (if skewness is observed) over time, the change over time will be summarized with graphs, and also analyzed using linear mixed-effects regression models with normalizing transformation if necessary.
Time frame: Pre-vaccine up to after 2 booster doses of STEMVAC vaccine (Up to 40 weeks)
Progression-free survival (PFS)
Will be analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) will be computed.
Time frame: From the start of treatment to the worsening of cancer as determined by primary treating oncologist or death whichever occurs first, assessed up to 3 years after completion of study treatment
Circulating tumor DNA (ctDNA)
Will evaluate persistence and level of ctDNA over time in peripheral blood with addition of STEMVAC at baseline, after completion of priming monthly doses, at booster vaccines, and at progression (end of study). Linear mixed-effects regression models with normalizing transformation (if necessary) will be employed to evaluate changes in ctDNA levels over time. Paired t test or Wilcoxon signed rank tests will be applied for pairwise comparisons (depending on the distribution) between time points.
Time frame: Up to 3 years after completion of study treatment
Elimination of cancer cells associated with epithelial to mesenchymal transformation (EMT)
Will determine whether STEMVAC immunization in addition to either endocrine therapy plus a CDK4/6 inhibitor or capecitabine results in elimination of cancer cells associated with EMT, as EMT proteins are targeted by this vaccine. Will determine EMT signature by gene expression profiling in baseline tumor (previously collected tumor biopsy) and compare with post-STEMVAC tumor biopsy. Gene expression profiles from biopsies before and after vaccination will be compared using paired t test or Wilcoxon signed-rank test (depending on the distribution) to determine if vaccination modulates the EMT gene signature in the tumor. Differential gene expression analysis or linear models will be used to analyze individual EMT gene expression levels.
Time frame: Up to 3 years after completion of study treatment
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