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

Primary Purpose

Breast Cancer, Breast Cancer Female, Breast Cancer, Male

Status

Active

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Dendritic Cell Vaccine (DC1)

Neoadjuvant Chemotherapy

Curative Surgery

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Immunotherapy, Dendritic Cell Vaccine, DC1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Sites / Locations

H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Lead In Phase - Arm A

Lead In Phase - Arm B

Expansion Phase

Arm Description

Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.

Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.

DC1 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).

Outcomes

Primary Outcome Measures

Expansion Phase Schedule Selection by Week 4

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).

Pathologic Complete Response (pCR) Rate

Pathologic complete response rate of participants treated in the Expansion Phase. Clinical efficacy will be defined by the pathologic complete response (pCR) rate, the percentage of patients who achieve pCR based on surgical pathology assessment.The definition of pathologic complete response (pCR) will be ypT0/is N0 (no residual viable invasive disease in the breast or nodes). Any response less than pCR will be scored as incomplete response or progression (if tumor size increases during neoadjuvant chemotherapy on physical exam/breast imaging).

Secondary Outcome Measures

Recurrence Free Survival (RFS)

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).

Full Information

NCT ID

NCT03387553

First Posted

December 19, 2017

Last Updated

September 21, 2023

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

United States Department of Defense

1. Study Identification

Unique Protocol Identification Number

NCT03387553

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 6, 2018 (Actual)

Primary Completion Date

August 29, 2026 (Anticipated)

Study Completion Date

August 29, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Immunotherapy, Dendritic Cell Vaccine, DC1

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Parallel Assignment

Model 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 vaccination schedules. Following accrual of this initial group of 12 patients, HER2 ELISPOT post 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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

31 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lead In Phase - Arm A

Arm Type

Active Comparator

Arm Description

Arm A: One Dendritic Cell Vaccine (DC1) per week x 3 weeks.

Arm Title

Lead In Phase - Arm B

Arm Type

Active Comparator

Arm Description

Arm B: Two DC1 vaccinations per week (given 3 days apart i.e., Mon and Thurs or Tues and Friday) x 3 weeks.

Arm Title

Expansion Phase

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Dendritic Cell Vaccine (DC1)

Other Intervention Name(s)

Immunotherapy

Intervention Description

Study Vaccine: Lead In Phase - Weekly as outlined in each treatment Arm. Expansion Phase - At the optimal schedule determined at the end of the Lead In Phase. Pre-surgery - Booster Vaccine at week 25 prior to receiving surgery. Post-surgery - Participants will receive a series of 3 booster intranodal study vaccines given once every 6 months.

Intervention Type

Drug

Intervention Name(s)

Neoadjuvant Chemotherapy

Other Intervention Name(s)

TCHP

Intervention Description

Upon completion of the 3 week series of vaccinations participants will then undergo neoadjuvant chemotherapy treatment with the TCH-P Taxotere (docetaxel), Carboplatin, Herceptin (trastuzumab), Perjeta (pertuzumab) standard of care neoadjuvant chemotherapy regimen given intravenously once every 3 weeks for up to 6 cycles. The treating physician will have the discretion to delay, modify, or shorten the neoadjuvant chemotherapy as per routine practice guidelines and physician discretion.

Intervention Type

Procedure

Intervention Name(s)

Curative Surgery

Intervention Description

Planned definitive curative surgery at 26 to 28 weeks.

Primary Outcome Measure Information:

Title

Expansion Phase Schedule Selection by Week 4

Description

Time Frame

By Week 4

Title

Pathologic Complete Response (pCR) Rate

Description

Time Frame

Week 26 to 28 - At post-surgical pathological assessment

Secondary Outcome Measure Information:

Title

Recurrence Free Survival (RFS)

Description

Time Frame

Up to 3 years post-surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants must have histologically confirmed clinical stage II or III ERPR- HER2+ (per CAP criteria) invasive 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Haten Soliman, M.D.

Organizational Affiliation

H. Lee Moffitt Cancer Center and Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

H. Lee Moffitt Cancer Center and Research Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

12. IPD Sharing Statement

Links:

URL

https://moffitt.org/clinical-trials-research/

Description

Moffitt Cancer Center Clinical Trials website

Learn more about this trial

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

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