Study of HER2 Directed Dendritic Cell (DC1) Vaccine + Weekly Paclitaxel, Trastuzumab & Pertuzumab
Phase 2
Recruiting
- Conditions
- HER2-positive Breast Cancer
- Interventions
- Procedure: Resection surgery
- Registration Number
- NCT05325632
- Brief Summary
The purpose of the study is to find out if an investigational drug called Dendritic Cell (DC1) vaccine added to standard neoadjuvant (given before main treatment) therapy can help people with HER2 (human epidermal growth factor receptor 2) positive breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 53
Inclusion Criteria
- Participants must have histologically confirmed clinical stage I- III, HER2+ (per ASCO/CAP criteria) invasive carcinoma of the breast. Primary tumor should measure at least 1 cm by clinical exam or radiologic tests
- Candidate for neoadjuvant chemotherapy with Paclitaxel, Trastuzumab, Pertuzumab regimen followed by standard of care local therapy as determined by the treating physician
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Participants must have normal organ and marrow function as defined per protocol.
- Cardiac ejection fraction within institutional normal limits by either Multigated Acquisition Scan (MUGA) or Echocardiogram 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
- Participants 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.
- Patients 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 (paclitaxel, trastuzumab, pertuzumab).
- Participants who are 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.
- Pregnant women and women who are breastfeeding.
- Participants with known congenital or acquired immune deficiency (including those patients who require systemic immunosuppressant drugs for autoimmune disease or organ transplant).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Lead In - Dose level 1 Paclitaxel Six participants will be treated at dose level 1: DC vaccine given at the dose of 50 million once per week for 6 weeks Lead In - Dose level 1 Resection surgery Six participants will be treated at dose level 1: DC vaccine given at the dose of 50 million once per week for 6 weeks Lead In: Dose Level 2 HER-2 pulsed DC1 Six participants will be treated at dose level 2: DC vaccine given at the dose of 100 million once per week for 6 weeks Lead In - Dose level 1 HER-2 pulsed DC1 Six participants will be treated at dose level 1: DC vaccine given at the dose of 50 million once per week for 6 weeks Lead In: Dose Level 2 Resection surgery Six participants will be treated at dose level 2: DC vaccine given at the dose of 100 million once per week for 6 weeks Expansion -Estrogen Receptor (ER) negative Resection surgery An additional 23 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) positive HER-2 pulsed DC1 An additional 24 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) positive Resection surgery An additional 24 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) negative HER-2 pulsed DC1 An additional 23 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Lead In - Dose level 1 Trastuzumab Six participants will be treated at dose level 1: DC vaccine given at the dose of 50 million once per week for 6 weeks Lead In - Dose level 1 Pertuzumab Six participants will be treated at dose level 1: DC vaccine given at the dose of 50 million once per week for 6 weeks Lead In: Dose Level 2 Paclitaxel Six participants will be treated at dose level 2: DC vaccine given at the dose of 100 million once per week for 6 weeks Lead In: Dose Level 2 Trastuzumab Six participants will be treated at dose level 2: DC vaccine given at the dose of 100 million once per week for 6 weeks Lead In: Dose Level 2 Pertuzumab Six participants will be treated at dose level 2: DC vaccine given at the dose of 100 million once per week for 6 weeks Expansion -Estrogen Receptor (ER) positive Trastuzumab An additional 24 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) positive Pertuzumab An additional 24 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) positive Paclitaxel An additional 24 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) negative Trastuzumab An additional 23 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) negative Paclitaxel An additional 23 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase). Expansion -Estrogen Receptor (ER) negative Pertuzumab An additional 23 participants will be enrolled at dose level 2 if determined to be safe in lead in phase to have a total of 28 evaluable participants for pathologic response assessment (including 6 pts from the lead in phase).
- Primary Outcome Measures
Name Time Method Lead in Phase: Immunogenicity of each dose level at 4 weeks Immunogenicity: will be characterized by quantifying CD4TH1 response via ELISPot. ELISPot is an enzyme-linked immunospot assay. It is a highly sensitive immunoassay that measures the frequency of cytokine-secreting cells at the single-cell level.
Expansion Phase: Pathologic Complete Response Rate at 12 months 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. Pathologic Complete Response defined as no residual invasive disease in the breast and nodes (ypT0/is N0) at definitive surgery after completion of protocol therapy. The pathologic response to treatment will be assessed by the pathologist. The "Residual Cancer Burden" (RCB) for each patient as described in the online calculator also will be evaluated per the pathologist. (http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=jsconvert3)
- Secondary Outcome Measures
Name Time Method Expansion Phase: Radiologic tumor response rate at completion of therapy at 12 months Radiologic tumor response rate measured by MRI
Expansion Phase: Immunogenicity at 12 months Immunogenicity: will be characterized by quantifying CD4TH1 response via ELISPot. ELISPot is an enzyme-linked immunospot assay. It is a highly sensitive immunoassay that measures the frequency of cytokine-secreting cells at the single-cell level.
Expansion Phase: Radiologic tumor response rate after 6 weeks at 6 weeks Radiologic tumor response rate measured by MRI
Recurrence Free Survival up to 5 years Recurrence free survival defined as the length of time after treatment that patient survives without any signs or symptoms of cancer.
Trial Locations
- Locations (1)
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States