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

January 24, 2024 updated by: Providence Health & Services

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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-

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: DPX-Survivac, Letrozole
Letrozole 2.5 mg po daily, DPX-Survivac 0.25 mL SC week 2 and Week 5
Biological: 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.
Drug: Letrozole 2.5mg
Aromatase inhibitor all arms will receive
Other Names:
  • Femara
Experimental: 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
Biological: 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.
Drug: Letrozole 2.5mg
Aromatase inhibitor all arms will receive
Other Names:
  • Femara
Radiation: XRT 10Gy x2
Directed radiation at week 4 for Arm B only
Experimental: 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
Biological: 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.
Drug: Letrozole 2.5mg
Aromatase inhibitor all arms will receive
Other Names:
  • Femara
Drug: Cyclophosphamide 50mg
oral chemotherapy used in the neoadjuvant setting for Arm C only
Other Names:
  • cytoxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
The safety assessment period begins with day 1 and ends within 30 days of surgical excision.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunogenicity of each therapeutic arm IFN-γ ELISPOT
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
assessed by IFN-γ ELISPOT in PBMC
throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery
Immunogenicity of each therapeutic arm GEO-Mx digital spatial profiler
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
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
throughout the study day 1, Day 8, Day 15, Day 29, Day 36, Week 7-9, Week 11, and 6 months post-surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Providence Health & Services

Investigators

  • Principal Investigator: Sasha Stanton, MD, Providence Health & Services

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 10, 2021

Primary Completion (Actual)

June 16, 2023

Study Completion (Estimated)

September 1, 2026

Study Registration Dates

First Submitted

May 17, 2021

First Submitted That Met QC Criteria

May 19, 2021

First Posted (Actual)

May 20, 2021

Study Record Updates

Last Update Posted (Estimated)

January 25, 2024

Last Update Submitted That Met QC Criteria

January 24, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P2100-SUR-S11

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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