Clinical Trials /

Neoadjuvant MEDI4736 Concomitant With Weekly Nab-paclitaxel and Dose-dense AC for Stage I-III Triple Negative Breast Cancer

NCT02489448

Description:

The purpose of the study is to address the following hypotheses: (i) Anti-PD-L1 therapy with MEDI4736 administered concomitantly with weekly nab-paclitaxel followed by MEDI4736 concomitant with ddAC neoadjuvant chemotherapy will induce higher pathologic complete response (pCR) rate (>55%) in triple negative breast cancer than historical pCR rates (30-40%) observed with chemotherapy alone. (ii) MEDI4736 can be safely co-administered at full dose with sequential with nab-paclitaxel (100mg/m2) and ddAC (60 mg/m2 and 600 mg/m2 respectively).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02489448

Trial Eligibility

Document

Title

  • Brief Title: Neoadjuvant MEDI4736 Concomitant With Weekly Nab-paclitaxel and Dose-dense AC for Stage I-III Triple Negative Breast Cancer
  • Official Title: Single Arm Neoadjuvant Phase I/II Study of MEDI4736 (Anti-PD-L1 Antibody) Concomitant With Weekly Nab-paclitaxel and Dose-dense Doxorubicin/Cyclophosphamide (ddAC) Chemotherapy for Clinical Stage I-III Triple Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 1409014537
  • NCT ID: NCT02489448

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
MEDI4736tremelimumab, anti-PD-L1 antibodyMEDI4736

Purpose

The purpose of the study is to address the following hypotheses: (i) Anti-PD-L1 therapy with MEDI4736 administered concomitantly with weekly nab-paclitaxel followed by MEDI4736 concomitant with ddAC neoadjuvant chemotherapy will induce higher pathologic complete response (pCR) rate (>55%) in triple negative breast cancer than historical pCR rates (30-40%) observed with chemotherapy alone. (ii) MEDI4736 can be safely co-administered at full dose with sequential with nab-paclitaxel (100mg/m2) and ddAC (60 mg/m2 and 600 mg/m2 respectively).

Detailed Description

      The primary objective of the Phase I portion of the trial is to assess the safety of MEDI4736
      combined with chemotherapy and determine if full dose of MEDI4736 can be administered
      concomitantly with full dose weekly nab-paclitaxel followed by dose-dense AC chemotherapies,
      respectively.

      The primary objective of the Phase II portion of the study is to estimate the pCR rate with
      MEDI4736 in combination with weekly nab-paclitaxel x 12 treatments followed by MEDI4736 in
      combination with ddAC x 4 treatments for estrogen receptor (ER), progesterone receptor (PR)
      and HER2 negative (triple negative, TNBC), clinical stage I-III breast cancer. Pathologic
      complete response is defined as the absence of residual invasive cancer on hematoxylin and
      eosin evaluation of the resected breast specimen and all sampled regional lymph nodes
      following completion of neoadjuvant systemic therapy (i.e. ypT0/Tis ypN0).

      Secondary objectives include: to assess the safety and toxicity of adding anti-PD-L1
      antibody, MEDI4736 to standard of care neoadjuvant chemotherapy in the Phase II portion of
      the trial. The study will also monitor for events of special clinical interest with a
      suspected auto-immunologic etiology including grade ≥3 colitis, hyperthyroidism,
      hypophysitis, hypothyroidism, pneumonitis, rash and anti-drug-antibody (ADA) immune complex
      disease (manifested by symptoms of arthralgias, abdominal pain, back pain, and vasculitis).

      Exploratory objectives include: to assess correlation between response to therapy and immune
      parameters of the tumor at baseline and post-treatment in patients who have residual cancer
      after therapy.

Trial Arms

NameTypeDescriptionInterventions
MEDI4736ExperimentalThe investigational product is MEDI4736 which will be supplied in glass vials containing 500 mg of liquid solution at a concentration of 50 mg/mL for intravenous (IV) administration. Routine, standard of care chemotherapy will be given together with the investigational product and will include weekly nab-paclitaxel x12 treatments followed by every two-week doxorubicin, cyclophosphamide (ddAC) x 4 treatments.
  • MEDI4736

Eligibility Criteria

        Inclusion Criteria:

          1. Newly diagnosed histologically confirmed stage I-III, ER, PR and HER2 negative
             invasive breast cancer as defined by the ASCO CAP guidelines for whom systemic
             chemotherapy would be indicated based on physician judgment following standard NCCN
             practice guidelines.

          2. Willing and able to provide written informed consent for voluntary participation in
             the trial.

          3. Willing to undergo a baseline tumor core needle biopsy and blood draws for correlative
             science studies.

          4. Eighteen years of age or older on the day of signing informed consent.

          5. Female subjects must either be of non-reproductive potential or must have a negative
             urine or serum pregnancy test upon study entry.

          6. Patients should have adequate organ function to tolerate chemotherapy, as defined by:

               -  peripheral granulocyte count of > 1,500/mm3

               -  platelet count > 100,000/mm3

               -  hemoglobin >9 g/dL

               -  total bilirubin < 1.5 x upper limit of normal (ULN)

               -  aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each < 1.5 x
                  ULN

               -  serum creatinine < 1.5 x ULN or serum creatinine clearance < 50mL/min

               -  INR/PT/PTT each < 1.5 x ULN

               -  TSH within normal limits

        Exclusion Criteria:

          1. Patients who underwent partial excisional biopsy or lumpectomy, segmental mastectomy
             or modified radical mastectomy or sentinel node.

          2. Patients for whom anthracycline, paclitaxel or antibody therapies are contraindicated.

          3. Patients with active autoimmune disease or documented autoimmune disease within 2
             years. Patients with hypothyroidism that is clinically stable and have normal TSH
             levels with hormone replacement, or patients with vitiligo or psoriasis not requiring
             treatment remain eligible for the study.

          4. Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative
             colitis).

          5. Patients with known active hepatitis B or C or HIV infection or with history of
             tuberculosis.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Pathologic Complete Response (pCR)
Time Frame:19 weeks
Safety Issue:
Description:Pathologic response will be assessed in the surgically resected cancer and lymph nodes after completion of all chemotherapy by the local pathologist as part of routine care. Pathologic complete response is defined as no invasive cancer in the resected breast tissue and lymph nodes (ypT0/Tis, ypN0).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Yale University

Trial Keywords

  • Breast Cancer

Last Updated

January 25, 2021