This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04895761
Recruitment Status : Active, not recruiting
First Posted : May 20, 2021
Last Update Posted : January 25, 2024
Sponsor:
Information provided by (Responsible Party):
Providence Health & Services

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: DPX-Survivac Drug: Letrozole 2.5mg Drug: Cyclophosphamide 50mg Radiation: XRT 10Gy x2 Phase 1

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study of Neoadjuvant DPX-Survivac, Aromatase Inhibition, and With/Without Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer
Actual Study Start Date : September 10, 2021
Actual Primary Completion Date : June 16, 2023
Estimated Study Completion Date : September 1, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: 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 Name: Femara

Drug: Cyclophosphamide 50mg
oral chemotherapy used in the neoadjuvant setting for Arm C only
Other Name: cytoxan


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Women with resectable, non-metastatic breast cancer
Accepts Healthy Volunteers:   No
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-

Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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): NCT04895761


Locations
Layout table for location information
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
Sponsors and Collaborators
Providence Health & Services
Investigators
Layout table for investigator information
Principal Investigator: Sasha Stanton, MD Providence Health & Services
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: Providence Health & Services
ClinicalTrials.gov Identifier: NCT04895761    
Other Study ID Numbers: P2100-SUR-S11
First Posted: May 20, 2021    Key Record Dates
Last Update Posted: January 25, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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
Keywords provided by Providence Health & Services:
HR+/HER2
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Letrozole
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
 Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists