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Neoadjuvant Dupilumab, Pembrolizumab, Paclitaxel, and Carboplatin in Locally Advanced Triple Negative Breast Cancer

ConditionsLocally Advanced Triple Negative Breast CancerTNBC - Triple-Negative Breast Cancer
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorRima Patel

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Dupilumab

    Drug

    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.

  • Pembrolizumab

    Drug

    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).

  • Paclitaxel

    Drug

    Paclitaxel 80mg/m2 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the treatment of patients with breast cancer.

  • Carboplatin

    Drug

    Carboplatin AUC 1.5 intravenous weekly for 12 weeks. Chemotherapy FDA-approved for the treatment of patients with breast cancer.

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: Patients with locally advanced TNBCExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Incidence of severe immune-related adverse events (irSAE)

Incidence of severe immune-related adverse events within 4 months of therapy. Immune related Severe Adverse Events (irSAE) are defined as: * Any Grade 4 immune-related AE with the exception of hypothyroidism * Any Grade 3 immune-related AE requiring permanent discontinuation of dupilumab and pembrolizumab * Any new Grade 3 or Grade 4 non-hematologic laboratory abnormality, if * medical intervention is required, or * the abnormality leads to hospitalization, or * the abnormality persists for \> 72 hours * Any non-hematologic AE which is considered severe or life-threatening and requires discontinuation of dupilumab and pembrolizumab * Any ≥ Grade 2 immune-mediated uveitis * Any immune-related AE resulting in persistent or significant disability/incapacity (substantial disruption of one's ability to conduct normal life functions) for a period of 30 days or greater * Grade 5 or life-threatening toxicity

Time frame
Within 4 months of therapy

Secondary outcomes

1

Proportion of patients with pathologic complete response (pCR) with 95 percent Wilson Score interval

Pathologic complete response (pCR) is defined as the lack of invasive cancer in the breast and axilla at time of surgical resection after neoadjuvant therapy. The research team will calculate the proportion of patients with pathologic complete response with 95 percent Wilson Score interval without continuity correction.

Time frame
During procedure, after 13 weeks of neoadjuvant therapy
2

Proportion of patients with residual cancer burden (RCB) categories 0 and 1 with 95 percent Wilson Score

Residual cancer burden (RCB) categories 0-1 comprise of patients who have achieved pCR (RCB 0) and have minimal tumor burden (RCB 1) after neoadjuvant therapy. The research team will calculate the proportion of patients with residual cancer burden categories 0 and 1 with 95 percent Wilson Score interval without continuity correction.

Time frame
After completion of neoadjuvant therapy (13 weeks)
3

Proportion of patients who did not experience an invasive breast cancer recurrence (Recurrence-Free Survival (RFS))

Recurrence-free survival (RFS) is measured as the proportion of patients who did not experience an invasive breast cancer recurrence in the ipsilateral breast or regional nodes, distant organ sites, or death from any cause for the specified time period. It is defined as time from start of treatment to occurrence of an invasive breast cancer recurrence in the ipsilateral breast or regional nodes, distant organ sites, or death from any cause. The research team will summarize using Kaplan-Meier method with 95 percent pointwise confidence intervals using complimentary log-log scale. Median RFS with 95 percent confidence interval will be calculated using Brookmeyer and Crowley method. Hazard ratios with 95 percent confidence interval will be estimated using Proportional Hazards Cox regression model.

Time frame
During procedure, after 13 weeks of neoadjuvant therapy
4

Overall Survival (OS)

Overall survival (OS) is defined as the time from the start of treatment until documented death from any cause. The research team will summarize using Kaplan-Meier method with 95 percent pointwise confidence intervals using complimentary log-log scale. Median RFS with 95 percent confidence interval will be calculated using Brookmeyer and Crowley method. Hazard ratios with 95 percent confidence interval will be estimated using the Cox Proportional Hazards regression model.

Time frame
After completion of neoadjuvant therapy (13 weeks)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Rima Patel

Lead sponsor

Icahn School of Medicine at Mount Sinai

Sponsor institution

Source ClinicalTrials.gov
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