Clinical Trials /

HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+Breast Cancer

NCT03387553

Description:

The purpose of this study is to learn more about how to treat patients with HER-2/neu positive invasive breast cancer (IBC). HER-2/neu is a type of protein that is known to be over-expressed in aggressive breast cancer. The study drug for this trial is DC1 study vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. This study vaccine is made from the participant's blood cells collected from a procedure called leukapheresis. Dendritic cells are immune cells that can tell the immune system to fight infection. In laboratory testing and from previous studies in participants, these cells may also help the immune system attack tumors such as breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+Breast Cancer
  • Official Title: A Pilot Study Utilizing a HER2 Directed Dendritic Cell Vaccine During Neoadjuvant Therapy of HER2+ Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: MCC-19337
  • NCT ID: NCT03387553

Conditions

  • Breast Cancer
  • Breast Cancer Female
  • Breast Cancer, Male
  • Invasive Breast Cancer
  • HER2-positive Breast Cancer
  • HER2 Positive Breast Carcinoma
  • Stage II Breast Cancer
  • Stage III Breast Cancer

Interventions

DrugSynonymsArms
Dendritic Cell Vaccine (DC1)ImmunotherapyLead In Phase - Arm A
Neoadjuvant ChemotherapyTCHPLead In Phase - Arm A

Purpose

The purpose of this study is to learn more about how to treat patients with HER-2/neu positive invasive breast cancer (IBC). HER-2/neu is a type of protein that is known to be over-expressed in aggressive breast cancer. The study drug for this trial is DC1 study vaccine which is a HER2-sensitized dendritic cell (DC) study vaccine. This study vaccine is made from the participant's blood cells collected from a procedure called leukapheresis. Dendritic cells are immune cells that can tell the immune system to fight infection. In laboratory testing and from previous studies in participants, these cells may also help the immune system attack tumors such as breast cancer.

Detailed Description

      The trial will consist of two phases. The first lead in phase will enroll 12 participants
      evenly divided into two arms (alternating enrollment) with different initial priming study
      vaccination schedules.

      Arm A: One DC1 study vaccination per week x 3 weeks. Arm B: Two DC1 study vaccinations per
      week (given 3 days apart for example Mon and Thurs or Tues and Friday) x 3 weeks.

      Following accrual of this initial group of 12 participants, HER2 ELISPOT post study
      vaccination responses will be assessed to determine which of the two sequences provides the
      greater increase in anti HER2 response at week 4 over baseline. This will determine which
      sequence will be used in the second expansion phase of accrual. If both arms are determined
      equal then Arm A will be selected as the default sequence.

      Second phase of accrual will consist of 14 additional participants to undergo study
      vaccination using the optimal schedule declared in the first phase of the trial. The trial
      will consist of two phases. The first lead in phase will enroll 12 participants evenly
      divided into two arms (alternating enrollment) with different initial priming study
      vaccination schedules.

      Arm A: One DC1 study vaccination per week x 3 weeks Arm B: Two DC1 study vaccinations per
      week (given 3 days apart for example Mon and Thurs or Tues and Friday) x 3 weeks.

      Following accrual of this initial group of 12 participants, HER2 ELISPOT post study
      vaccination responses will be assessed to determine which of the two sequences provides the
      greater increase in anti HER2 response at week 4 over baseline. This will determine which
      sequence will be used in the second expansion phase of accrual. If both arms are determined
      equal then Arm A will be selected as the default sequence.

      Second phase of accrual will consist of 14 additional participants to undergo study
      vaccination using the optimal schedule declared in the first phase of the trial.
    

Trial Arms

NameTypeDescriptionInterventions
Lead In Phase - Arm AActive ComparatorArm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.
  • Neoadjuvant Chemotherapy
Lead In Phase - Arm BActive ComparatorArm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.
  • Neoadjuvant Chemotherapy
Expansion PhaseExperimentalDC1 vaccinations according to optimal vaccination schedule. Participants will receive a booster intranodal study vaccine at week 25 prior to receiving surgery. Participants will then undergo definitive curative surgery following completion of the neoadjuvant therapy, additional adjuvant locoregional/systemic therapy (as deemed appropriate by their treating physicians).
  • Neoadjuvant Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Participants must have histologically confirmed clinical stage II or III ERPR- HER2+
             (per CAP criteria) invasive ductal carcinoma of the breast

          -  Medically and surgically appropriate to undergo neoadjuvant chemotherapy with TCH-P
             Taxotere (docetaxel), Carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab)
             regimen followed by standard of care local therapy as determined by their treating
             physician

          -  Age ≥18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than 2

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocytes ≥3,000/μL

               -  absolute neutrophil count ≥1,500/μL

               -  platelets ≥100,000/μL

               -  total bilirubin within normal institutional limits

               -  AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of
                  normal

               -  creatinine within normal institutional limits - OR -

               -  creatinine clearance ≥60 mL/min/1.73 m^2 for patients with creatinine levels
                  above institutional normal

          -  Cardiac ejection fraction within institutional normal limits by either MUGA or ECHO at
             baseline.

          -  Women of child-bearing potential and their male partners must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation. Should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately. Sexually active male participants should use a barrier
             method or exercise abstinence during chemotherapy administration until surgery.

          -  Ability to understand and the willingness to sign a written informed consent document.

        Exclusion Criteria:

          -  Patients with inflammatory breast cancer, widespread locally advanced unresectable
             disease involving the chest wall/nodal basins in which a curative surgical resection
             cannot be performed, or those in whom de novo metastatic disease is suspected or
             confirmed

          -  May not be receiving any other investigational agents for the treatment of their
             breast cancer.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to the study vaccine components and any of the chemotherapy drugs
             (docetaxel, carboplatin, trastuzumab, pertuzumab)

          -  Unwilling or unable to undergo an apheresis for production of their vaccine

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Women who are pregnant or breastfeeding

          -  Known congenital or acquired immune deficiency (including those patients who require
             systemic immunosuppressant drugs for autoimmune disease or organ transplant).

          -  Pre-existing peripheral neuropathy that would limit treatment with taxanes and
             platinum agents
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Expansion Phase Schedule Selection by Week 4
Time Frame:By Week 4
Safety Issue:
Description:Immunogenicity of HER2 DC Vaccine per treatment Arm, based on week 4 ELISPOTs. Three metrics of CD4+ Th1 response will be computed for each patient, (a) overall anti-HER2 responsivity (i.e., if patient demonstrates a positive ELISPOT response to >1 peptide, (b) response repertoire (i.e., number of reactive peptides) and (c) cumulative response (total SFC/10^6 cells across 6 peptides). The primary immunogenicity outcome will be the cumulative response at week 4 (week after completion of all vaccinations).

Secondary Outcome Measures

Measure:Recurrence Free Survival (RFS)
Time Frame:Up to 3 years post-surgery
Safety Issue:
Description:Recurrence-free survival (RFS) will be defined as the time from first vaccination to documented recurrence (any breast event), death due to any cause or last patient contact that documents recurrence-free status (i.e., a clinic or scan date).

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • Immunotherapy
  • Dendritic Cell Vaccine
  • DC1

Last Updated

April 9, 2018