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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Yale University
Sponsor:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT02489448
First received: July 1, 2015
Last updated: July 12, 2016
Last verified: July 2016
  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).

Condition Intervention Phase
Breast Neoplasms
Drug: MEDI4736
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Pathologic Complete Response (pCR) [ Time Frame: 19 weeks ]
    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).


Estimated Enrollment: 61
Study Start Date: November 2015
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MEDI4736

The 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.

Drug: MEDI4736

The 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.

Other Name: tremelimumab, anti-PD-L1 antibody

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02489448

Contacts
Contact: Courtney Frederick, RN (203) 785-6128 courtney.frederick@yale.edu
Contact: Noelle M Sowers, RN (203) 737-8309 noelle.sowers@yale.edu

Locations
United States, Connecticut
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06511
Contact: Laurene Goode-Gade    203-737-8309    Laurene.goode-gade@yale.edu   
Principal Investigator: Lajos Pusztai, MD, D.Phil.         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Lajos Pusztai, MD, D. Phil. Yale School of Medicine
  More Information

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02489448     History of Changes
Other Study ID Numbers: 1409014537
Study First Received: July 1, 2015
Last Updated: July 12, 2016

Keywords provided by Yale University:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Tremelimumab
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on April 24, 2017