Clinical Trials /

Preoperative Lenvatinib Plus Pembrolizumab in Early-Stage Triple-Negative Breast Cancer (TNBC)

NCT04427293

Description:

This is a single arm, window of opportunity study in which participants with previously untreated triple negative breast cancers (TNBC) who are candidates for potentially curative surgery will receive one 21-day cycle of therapy prior to surgery, consisting of lenvatinib 12 mg daily, days 1 through 14, and pembrolizumab 200 mg IV on day 1

Related Conditions:
  • Invasive Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Preoperative Lenvatinib Plus Pembrolizumab in Early-Stage Triple-Negative Breast Cancer (TNBC)
  • Official Title: BRE-03: Window of Opportunity Trial of Preoperative Lenvatinib Plus Pembrolizumab in Early-Stage Triple-Negative Breast Cancer (TNBC)

Clinical Trial IDs

  • ORG STUDY ID: 2020-0232
  • NCT ID: NCT04427293

Conditions

  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
LenvatinibOpen Label
PembrolizumabOpen Label

Purpose

This is a single arm, window of opportunity study in which participants with previously untreated triple negative breast cancers (TNBC) who are candidates for potentially curative surgery will receive one 21-day cycle of therapy prior to surgery, consisting of lenvatinib 12 mg daily, days 1 through 14, and pembrolizumab 200 mg IV on day 1

Detailed Description

      This is a single arm, window of opportunity study in which participants with previously
      untreated triple negative breast cancers (TNBC) who are candidates for potentially curative
      surgery will receive one 21-day cycle of therapy prior to surgery, consisting of lenvatinib
      12 mg daily, days 1 through 14, and pembrolizumab 200 mg IV on day 1. Participants will
      undergo surgical resection of the primary breast tumor 7-10 days after the last dose of
      lenvatinib. Post-operative adjuvant therapies will be at the discretion of the treating
      oncologist. Post-Surgery Follow-Up information will be collected at assessments at 3 months
      post-op and after that every 6 months until 5 years after surgery
    

Trial Arms

NameTypeDescriptionInterventions
Open LabelExperimentalAll participants will receive one 21-day cycle of therapy prior to surgery, consisting of lenvatinib 12 mg daily, days 1 through 14, and pembrolizumab 200 mg IV on day 1
  • Lenvatinib
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years of age at time of consent

          2. Histologically confirmed invasive breast carcinoma documented by core needle biopsy or
             incisional biopsy (excisional biopsy is not allowed). AJCC 8th edition clinical stage
             T1b-T2/N0-N1/M0 by physical exam or radiologic studies

          3. Must be candidates for curative surgical resection

          4. Have an FFPE diagnostic core biopsy specimen available that is determined by the study
             pathologist to be adequate for planned analyses

          5. Definitive surgical excision of the primary breast tumor (either partial mastectomy or
             total mastectomy) and ipsilateral axillary lymph node sampling (sentinel lymph node
             biopsy or axillary dissection) is planned following completion of preoperative
             chemotherapy.

          6. Estrogen Receptor (ER)- and Progesterone Receptor (PR)-negative as determined by
             immunohistochemistry (IHC), and Human Epidermal Growth Factor Receptor (HER)2-negative
             (triple-negative) cancer of the breast

             Triple-negative tumors are defined as:

               -  Less than or equal to 10% of tumor cells staining for ER and for PR by
                  immunohistochemistry (IHC)

               -  HER2-negative, as defined by ASCO/CAP guidelines55

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 within 30
             days prior to study registration

          8. Demonstrate adequate organ function as defined in the table below; all screening labs
             to be obtained within 30 days prior to registration Hematological Leukocytes
             ≥2,500/mm3 Platelet count ≥ 100,000/mm3 Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
             Hemoglobin (Hgb) ≥ 9.0 g/dL Renal Creatinine/Calculated creatinine clearance (CrCl) Cr
             < 1.5 x upper limit of normal (ULN) or CrCl ≥ 50 mL/min using the Cockcroft-Gault
             formula Hepatic Bilirubin Bilirubin ≤ 1.5 × ULN. Subjects with Gilbert's syndrome may
             have a bilirubin > 1.5 × ULN, if no evidence of biliary obstruction exists Aspartate
             aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN

          9. No evidence of distant metastases (M0 as per AJCC staging guidelines)

         10. Provided written informed consent and HIPAA authorization for release of personal
             health information, approved by an Institutional Review Board (IRB)

         11. NOTE: HIPAA authorization may be included in the informed consent or obtained
             separately

         12. Women of childbearing potential (WOCP) must not be pregnant or breast-feeding. A
             negative serum or urine pregnancy test is required within 14 days of study
             registration. If the urine test cannot be confirmed as negative, a serum pregnancy
             test will be required

         13. Women of childbearing potential (WOCP) must be willing to use two effective methods of
             birth control such as an oral, implantable, injectable, or transdermal hormonal
             contraceptive, an intrauterine device (IUD), use of a double barrier method (condoms,
             sponge, diaphragm, or vaginal ring with spermicidal jellies or cream), or total
             abstinence for the course of the study until 120 days after the last dose of study
             drug NOTE: Women are considered to be of childbearing potential unless they are
             postmenopausal (≥45 years of age and has not had menses for greater than 12
             consecutive months or bilateral oophorectomy) or surgically sterile (bilateral tubal
             ligation or hysterectomy) or not heterosexually active for the duration of the study
             and at least 120 days after the last dose of study drug

         14. As determined by the enrolling physician or protocol designee, ability of the subject
             to understand and comply with study procedures for the entire length of the study

        Exclusion Criteria:

          1. Requiring standard neoadjuvant chemotherapy

          2. Active infection requiring systemic therapy

          3. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
             mother is being treated on study)

          4. Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic
             therapy, radiotherapy directed towards the primary breast tumor and/or ipsilateral
             axillary lymph nodes or investigational agents) with therapeutic intent for the
             current breast cancer

          5. Previous treatment with lenvatinib or any immune checkpoint inhibitor within the past
             2 years

          6. Treatment with any investigational drug within 14 days prior to registration or within
             5 half-lives of the investigational product, whichever is longer

          7. Major surgery within 14 days prior to registration or has not recovered from major
             side effects of a major surgery (tumor biopsy and placement of an indwelling venous
             access device are not considered major surgery)

          8. Any prior or concurrent malignancy whose natural history or treatment has the
             potential to interfere with the safety or efficacy assessment of this investigational
             regimen, as determined by the treating Medical Oncologist.

          9. Known history of AIDS (HIV testing is not mandatory). HIV-positive individuals on
             active HARRT therapy with virologic suppression (defined as an HIV-1 RNA level below
             the lower limit of detection of the assay used) within 90 days of study enrollment and
             a CD4 cell count >500 cells/mm3 on the most recent determination are eligible for the
             study

         10. . Subjects with any of the following conditions:

               -  History of abdominal fistula, gastrointestinal perforation, or intra- abdominal
                  abscess within 28 days prior to registration

               -  History of cerebrovascular accident (CVA) or transient ischemic attack within 6
                  months prior to registration

               -  History of acute coronary syndromes (including myocardial infarction, unstable
                  angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
                  symptomatic pericarditis within 6 months prior to registration

               -  Symptomatic congestive heart failure (New York Heart Association III-IV) or
                  documented current left ventricular (LV) systolic dysfunction with left
                  ventricular ejection fraction (LVEF) <50% on most recent assessment of LV
                  function

               -  Clinically significant cardiac ventricular arrhythmias (e.g. sustained
                  ventricular tachycardia/ventricular fibrillation) or high-grade AV block (e.g.
                  bifascicular block, Mobitz type II and third-degree AV block) unless a pacemaker
                  is in place

               -  Any concurrent severe and/or uncontrolled medical condition that would, in the
                  investigator's judgment, cause unacceptable safety risks, contraindicate subject
                  participation in the clinical study or compromise compliance with the protocol

         11. Any condition that, in the opinion of the investigator, might jeopardize the safety of
             the patient or interfere with protocol compliance

         12. Any mental or medical condition that prevents the patient from giving informed consent
             or participating in the trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Evaluate the effectiveness of preoperative anti-vascular endothelial growth factor receptor (VEGFR) therapy and immune checkpoint blockade on infiltration of CD8+ tumor infiltrating lymphocytes (TILs) (CD45RA-/CD8+/FoxP3-) in primary tumors from patients
Time Frame:2 years
Safety Issue:
Description:Measuring the presence of a T-cell inflamed TME, characterized by infiltration of CD8+ TILs

Secondary Outcome Measures

Measure:Evaluate clinical response to preoperative anti-VEGFR therapy and immune checkpoint blockade based on pathologic complete response and changes in the Ki-67 index in patients with early-stage TNBC.
Time Frame:At the point of surgery
Safety Issue:
Description:Reviewing pathology report
Measure:Evaluate treatment tolerability of preoperative anti-VEGFR therapy and immune checkpoint blockade assessed by failure to completed planned course of neoadjuvant chemotherapy in patients with early-stage TNBC
Time Frame:30 days post treatment
Safety Issue:
Description:Assessing for adverse events (e.g., infections) using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Illinois at Chicago

Last Updated

June 8, 2020