Clinical trial NCT03387553: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
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
Keywords: Immunotherapy
Dendritic Cell Vaccine
DC1
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2018-01-02
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Expansion Phase Schedule Selection by Week 4
timeFrame: By Week 4
measure: Pathologic Complete Response (pCR) Rate
timeFrame: Week 26 to 28 - At post-surgical pathological assessment
Secondary outcomes:
measure: Recurrence Free Survival (RFS)
timeFrame: Up to 3 years post-surgery
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Haten Soliman, M.D.
role: PRINCIPAL_INVESTIGATOR
References: