Neoadjuvant DPX-Survivac Aromatase Inhibition, Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer
NCT ID: NCT04895761
Last Updated: 2025-03-10
Study Results
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Basic Information
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ACTIVE_NOT_RECRUITING
PHASE1
6 participants
INTERVENTIONAL
2021-09-10
2026-09-01
Brief Summary
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Detailed Description
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Primary Objective
1\) Safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with cyclophosphamide in stage I to III HR+HER2- breast cancer Secondary Objectives
1. Immunogenicity of each arm, assessed by IFN-γ ELISPOT in PBMC.
2. Immunogenicity of each arm, assessed by GEO-Mx digital spatial profiler evaluation of FFPE tissue and TCRβ evaluation for surviving-specific T cells in the tumor.
Exploratory Objectives
1. Evaluation of the % TIL in the biopsy specimen and at the time of surgery within/between arms
2. Evaluation of the Ki67 changes between the biopsy and at time of surgery within/between arms
3. Comparison of immunogenicity, TIL change, and Ki67 change across arms
4. Epitope spreading within/between arms
5. Evaluation of Triseq (germline, whole exome sequencing, and RNAseq) of the tumor immune environment within/between arms
6. Evaluation of immune environment using multi-parameter immunohistochemistry within/between arms
7. Evaluation by experimental MRI in arm that adds radiation
8. Evaluation of survivin-specific MHC-tetramer staining in PBMC
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: DPX-Survivac, Letrozole
Letrozole 2.5 mg po daily, DPX-Survivac 0.25 mL SC week 2 and Week 5
DPX-Survivac
DPX is a novel formulation that when combined with target antigens acts to activate T cells. It is a lipid-based formulation that creates a long lasting depot at the site of injection, forcing an "active uptake" by antigen presenting cells (APCs). APCs traffic to regional lymph nodes where naïve T cells are activated, inducing strong and sustained immune responses. All arms will receive DPX-Survivac on weeks 2 and 5.
Letrozole 2.5mg
Aromatase inhibitor all arms will receive
Arm B: DPX-Survivac, Letrozole, Radiation
Letrozole 2.5 mg po daily, XRT 10 Gy x 2, DPX-Survivac 0.25 mL SC week 2 and Week 5
DPX-Survivac
DPX is a novel formulation that when combined with target antigens acts to activate T cells. It is a lipid-based formulation that creates a long lasting depot at the site of injection, forcing an "active uptake" by antigen presenting cells (APCs). APCs traffic to regional lymph nodes where naïve T cells are activated, inducing strong and sustained immune responses. All arms will receive DPX-Survivac on weeks 2 and 5.
Letrozole 2.5mg
Aromatase inhibitor all arms will receive
XRT 10Gy x2
Directed radiation at week 4 for Arm B only
Arm C: DPX-Survivac, Letrozole, cyclophosphamide
Letrozole 2.5 mg po daily, cyclophosphamide 50 mg po BID, DPX-Survivac 0.25 mL SC week 2 and Week 5
DPX-Survivac
DPX is a novel formulation that when combined with target antigens acts to activate T cells. It is a lipid-based formulation that creates a long lasting depot at the site of injection, forcing an "active uptake" by antigen presenting cells (APCs). APCs traffic to regional lymph nodes where naïve T cells are activated, inducing strong and sustained immune responses. All arms will receive DPX-Survivac on weeks 2 and 5.
Letrozole 2.5mg
Aromatase inhibitor all arms will receive
Cyclophosphamide 50mg
oral chemotherapy used in the neoadjuvant setting for Arm C only
Interventions
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DPX-Survivac
DPX is a novel formulation that when combined with target antigens acts to activate T cells. It is a lipid-based formulation that creates a long lasting depot at the site of injection, forcing an "active uptake" by antigen presenting cells (APCs). APCs traffic to regional lymph nodes where naïve T cells are activated, inducing strong and sustained immune responses. All arms will receive DPX-Survivac on weeks 2 and 5.
Letrozole 2.5mg
Aromatase inhibitor all arms will receive
Cyclophosphamide 50mg
oral chemotherapy used in the neoadjuvant setting for Arm C only
XRT 10Gy x2
Directed radiation at week 4 for Arm B only
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Women with resectable, non-metastatic breast cancer that is \>1 cm, hormone receptor positive, HER2 negative, Ki67\>10%.
3. HER2 negative is defined as:
0-1+ HER2 expression by immunohistochemistry (IHC) OR Fluorescence in situ hybridization (FISH) negative OR HER2 2+ and FISH negative
4. Patients must be at least 28 days post systemic steroids prior to enrollment.
5. Patients must be at least 18 years of age.
6. Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status Score of ≤ 1
7. Adequate laboratory values within 30 days of enrollment defined as follows:
1. White blood cell (WBC) ≥ 3000/mm3
2. Hemoglobin (Hgb) ≥ 9 g/dL
3. Neutrophil count ≥ 1500/mm3
4. Lymphocyte count ≥ 1000/mm3
5. Platelet count ≥ 75,000/mm3
6. Serum creatinine ≤ 2.0 mg/dL or creatinine clearance \> 60 ml/min
7. Total bilirubin ≤ 1.5 mg/dL
8. Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) ≤ 2 times the ULN-
8. Patients must have recovered from major infections and, in the opinion of the investigator, do not have any significant active concurrent medical illnesses precluding protocol treatment.
9. The effects of DPX-Survivac on the developing human fetus are unknown. Women on the trial should be post-menopausal based on the NCCN definition of menopause
10. For patients in Arm B only, they must be able to undergo MR imaging as determined by treating physician using the standard Radiation Oncology MR screening process
Exclusion Criteria
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to DPX-Survivac.
3. Pregnant and pre-menopausal women are excluded from this study because to keep anti-endocrine therapy consistent between patients.
4. Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
5. Uncontrolled autoimmune disease. Autoimmune disease allowed if controlled (with or without treatment) for the last 12 months.
6. Patients may not have received or plan to receive neoadjuvant systemic chemotherapy. 7) Patients unable to receive an aromatase inhibitor
8\) Prior radiation to the affected breast 9) Previous cancers except for non-melanoma skin cancers or high risk cervical lesions in the past 5 years.
10\) Previous breast cancer, tamoxifen, or aromatase inhibitor use. 11) Previous investigational immune therapy use-
18 Years
FEMALE
No
Sponsors
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Providence Health & Services
OTHER
Responsible Party
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Principal Investigators
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Sasha Stanton, MD
Role: PRINCIPAL_INVESTIGATOR
Providence Health & Services
Locations
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Providence Portland Medical Center
Portland, Oregon, United States
Countries
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References
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Other Identifiers
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P2100-SUR-S11
Identifier Type: -
Identifier Source: org_study_id
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