Trial Title:
Neoadjuvant Dupilumab, Pembrolizumab, Paclitaxel, and Carboplatin in Locally Advanced Triple Negative Breast Cancer
NCT ID:
NCT06637306
Condition:
Locally Advanced Triple Negative Breast Cancer
TNBC - Triple-Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Paclitaxel
Carboplatin
Pembrolizumab
Conditions: Keywords:
Dupilumab
Pembrolizumab
IL-4 Receptor Antagonist
Breast Cancer
Triple Negative
Locally Advanced
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Open Label, Single Arm Trial.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dupilumab
Description:
Dupilumab 600mg subcutaneous initial loading dose, 300mg for subsequent doses;
administered every 3 weeks for 4 cycles. Immunotherapy drug FDA approved to treat
patients with eczema, asthma, chronic rhinosinusitis with nasal polyps, and eosinophilic
esophagitis. Investigational/not yet FDA approved to treat patients with breast cancer.
Arm group label:
Patients with locally advanced TNBC
Other name:
DUPIXENT
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab 200mg intravenous every 3 weeks for 4 cycles and one 400mg intravenous dose
one week following completion of chemotherapy. Cancer immunotherapy drug FDA approved for
the treatment of high-risk, early-stage, triple-negative breast cancer (TNBC).
Arm group label:
Patients with locally advanced TNBC
Other name:
KEYTRUDA
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Paclitaxel 80mg/m2 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the
treatment of patients with breast cancer.
Arm group label:
Patients with locally advanced TNBC
Other name:
TAXOL
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin AUC 1.5 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the
treatment of patients with breast cancer.
Arm group label:
Patients with locally advanced TNBC
Summary:
Pilot trial of the IL-4 receptor antagonist dupilumab plus pembrolizumab, paclitaxel, and
carboplatin in locally advanced triple negative breast cancer (TNBC).
Primary Objective: To assess the safety of neoadjuvant dupilumab and pembrolizumab plus
weekly paclitaxel and carboplatin as measured by the proportion of severe immune-related
adverse events (irAEs) in patients with locally advanced TNBC.
Secondary Objectives: To determine the rates of pathologic complete response with the
addition of dupilumab to NAC and pembrolizumab; to determine the rate of residual cancer
burden 0-1; to estimate the recurrence-free survival and overall survival; to assess the
toxicity of the combination of dupilumab, pembrolizumab, and paclitaxel-carboplatin.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with pathologically confirmed diagnosis of triple negative breast cancer,
as defined by the most recent ASCO/CAP guidelines.
- Patients must have previously untreated, localized TNBC with either tumor size ≥ 2
centimeters (T2-4N0) or lymph node involvement with at least a 1cm tumor
(T1c-T4N1-3).
- Patients must have previously untreated disease with no prior definitive breast
surgery, radiation therapy, or systemic chemotherapy with therapeutic intent for
this breast cancer.
- Patients must be eligible to receive chemotherapy agents in the study including
paclitaxel and carboplatin.
- Patients must be willing and able to provide blood samples at the time points
indicated in the study calendar.
- Patients must be willing and able to have core needle biopsies of tumor prior to
initiation of treatment. Should patients undergo pre-treatment or on-treatment
biopsy procedure and inadequate number of biopsies are obtained, they may proceed
with initiation/continuation of treatment at the discretion of the investigator and
treating physician.
- Age ≥ 18 years.
- ECOG performance status 0-1.
- Adequate organ and marrow function as defined below:
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 100,000/mcl
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal
- creatinine within normal institutional limits
- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry, for the duration of study participation, and for 6 months
following completion of therapy. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately.
A female of child-bearing potential is any woman (regardless of sexual orientation,
having undergone a tubal ligation, or remaining celibate by choice) who meets the
following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has
had menses at any time in the preceding 12 consecutive months).
- Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or any treatment with therapeutic intent for the breast cancer.
- Patients may not be receiving any other investigational agents.
- Patients who have any distant metastases and considered to have Stage IV disease.
- Patients who have a diagnosis of immunodeficiency or are receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of trial treatment. Patients on chronic steroids (more than 4 weeks at
stable dose) equivalent to ≤ 10mg prednisone will not be excluded.
- Patients with active autoimmune disease that has required systemic treatment in the
past 1 year (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is acceptable.
- History or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating Investigator.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to carboplatin, paclitaxel, dupilumab or pembrolizumab used in
study. Documented allergic or hypersensitivity response to any protein therapeutics
(e.g., recombinant proteins, vaccines, intravenous immune globulins, monoclonal
antibodies, receptor traps).
- HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART)
regimen, or with <350 CD4+ T cells/microliter in the peripheral blood.
- Known active Hepatitis B (e.g., HBV detected by PCR or active Hepatitis C (e.g., HCV
RNA [qualitative] is detected). Patients with hepatitis B (HepBsAg+) who have
controlled infection (serum hepatitis B virus DNA PCR that is below the limit of
detection AND receiving anti-viral therapy for hepatitis B) are permitted. Patients
with controlled infections must undergo periodic monitoring of HBV DNA. Patients
must remain on anti-viral therapy for at least 6 months beyond the last dose of
investigational study drug.
- Known, untreated helminth infections. Patients with prior history of a helminth
infection who were fully treated are permitted.
- History of allogeneic hematopoietic cell transplantation or solid organ
transplantation.
- Receipt of a live vaccine within 30 days of planned start of study medication.
- History of irAE in response to prior immunotherapy that has not improved to a Grade
0 or 1; this does not include chronic conditions such as endocrinopathies which can
be treated with hormone replacement therapy.
- History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis,
organizing pneumonia) or active, noninfectious pneumonitis attributed to prior use
of cancer immunotherapy that required immune-suppressive doses of glucocorticoids to
assist with management. History of radiation pneumonitis treated with
glucocorticoids.
- 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.
- Patients must not be pregnant or nursing due to the potential for congenital
abnormalities and the potential of this regimen to harm nursing infants.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mount Sinai Health System
Address:
City:
New York
Zip:
10029
Country:
United States
Contact:
Last name:
Katherine Vandris
Email:
Katherine.Vandris@mssm.edu
Contact backup:
Last name:
Rima Patel
Start date:
December 1, 2024
Completion date:
June 1, 2027
Lead sponsor:
Agency:
Rima Patel
Agency class:
Other
Source:
Icahn School of Medicine at Mount Sinai
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06637306
