Clinical Trials /

Neoadjuvant DPX-Survivac Aromatase Inhibition, Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

NCT04895761

Description:

The study seeks to establish the 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. There will be sequential enrollment into 3 arms with an anticipated N=6 participants per arm for N=18 participants in total. All participants will receive letrozole 2.5 mg daily during the 6 weeks of neoadjuvant therapy. Neoadjuvant therapy occurs weeks 1-6, with standard of care surgery taking place week 7 to 9.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant DPX-Survivac Aromatase Inhibition, Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer
  • Official Title: Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: P2100-SUR-S11
  • NCT ID: NCT04895761

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
DPX-SurvivacArm A: DPX-Survivac, Letrozole
Letrozole 2.5mgFemaraArm A: DPX-Survivac, Letrozole
Cyclophosphamide 50mgcytoxanArm C: DPX-Survivac, Letrozole, cyclophosphamide

Purpose

The study seeks to establish the 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. There will be sequential enrollment into 3 arms with an anticipated N=6 participants per arm for N=18 participants in total. All participants will receive letrozole 2.5 mg daily during the 6 weeks of neoadjuvant therapy. Neoadjuvant therapy occurs weeks 1-6, with standard of care surgery taking place week 7 to 9.

Detailed Description

      Women with hormone receptor positive, HER2-negative (HR+/HER2-) breast cancer with large
      tumors or positive lymph nodes have low response rates with neoadjuvant chemotherapy.
      Survivin is overexpressed in HR+HER2- breast cancer. Increasing tumor-specific Th1 immunity
      by administration of DPX-Survivac may alter the immune environment of these tumors. Radiation
      is a standard component of breast cancer therapy causing a reduction in local recurrences and
      improved breast cancer specific survival. Low dose cyclophosphamide can deplete regulatory
      T-cells without altering levels of effector T-cells. The investigators predict that combining
      a vaccine targeting Survivin, overexpressed in HR+HER2- tumors, with other immune modulating
      therapies such as radiation or low dose cyclophosphamide can enhance the efficacy of
      DPX-Survivac.

      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
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: DPX-Survivac, LetrozoleExperimentalLetrozole 2.5 mg po daily, DPX-Survivac 0.25 mL SC week 2 and Week 5
  • DPX-Survivac
  • Letrozole 2.5mg
Arm B: DPX-Survivac, Letrozole, RadiationExperimentalLetrozole 2.5 mg po daily, XRT 10 Gy x 2, DPX-Survivac 0.25 mL SC week 2 and Week 5
  • DPX-Survivac
  • Letrozole 2.5mg
Arm C: DPX-Survivac, Letrozole, cyclophosphamideExperimentalLetrozole 2.5 mg po daily, cyclophosphamide 50 mg po BID, DPX-Survivac 0.25 mL SC week 2 and Week 5
  • DPX-Survivac
  • Letrozole 2.5mg
  • Cyclophosphamide 50mg

Eligibility Criteria

        Inclusion Criteria:

          1. Patients must provide informed consent prior to any study-specific procedures and be
             able to understand and be willing to sign an informed consent document. Results of
             standard-of-care tests or examinations performed prior to obtaining informed consent
             and prior to treatment may be used for screening assessments rather than repeating
             such evaluations if within 30 day of day 1.

          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:

          1. Patients may not be receiving any other investigational agents or on concurrent
             clinical trials while on during the clinical trial period.

          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-
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants without the following safety events: TASAEs, persistent grade III/IV TAAEs, or toxicity-related delays in curative-intent surgery. Toxicity graded by CTCAE v5.0 and monitoring of AEs performed per FDA and NCI guidelines.
Time Frame:The safety assessment period begins with day 1 and ends within 30 days of surgical excision.
Safety Issue:
Description:yes/no outcome variable, ascertained for each individual subject, and reported as a binomial proportion for each arm. Safety will be reported for all subjects who receive at least one dose of drug/radiation/study therapy

Secondary Outcome Measures

Measure:Immunogenicity of each therapeutic arm
Time Frame:throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery
Safety Issue:
Description:assessed by IFN-γ ELISPOT in PBMC
Measure:Immunogenicity of each therapeutic arm
Time Frame:throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery
Safety Issue:
Description:assessed by GEO-Mx digital spatial profiler evaluation of Formalin-Fixed, parafin-embedded (FFPE) tumor and TCRβ evaluation for surviving-specific T cells in the tumor

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Providence Health & Services

Trial Keywords

  • HR+/HER2

Last Updated

May 20, 2021