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

Primary Purpose

Breast Neoplasms

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MEDI4736
Sponsored by
Yale University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Neoplasms focused on measuring Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Yale School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MEDI4736

Arm Description

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.

Outcomes

Primary Outcome Measures

Pathologic Complete Response (pCR)
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). The outcome was changed from 19 weeks at the time of results entry as the treatment period was actually 20 weeks and the outcome was assessed 4-6 weeks after treatment when surgery took place.

Secondary Outcome Measures

Full Information

First Posted
July 1, 2015
Last Updated
October 24, 2022
Sponsor
Yale University
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1. Study Identification

Unique Protocol Identification Number
NCT02489448
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
November 2015 (undefined)
Primary Completion Date
June 15, 2021 (Actual)
Study Completion Date
August 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Neoplasms
Keywords
Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MEDI4736
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MEDI4736
Other Intervention Name(s)
tremelimumab, anti-PD-L1 antibody
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pathologic Complete Response (pCR)
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). The outcome was changed from 19 weeks at the time of results entry as the treatment period was actually 20 weeks and the outcome was assessed 4-6 weeks after treatment when surgery took place.
Time Frame
Up to 26 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Willing and able to provide written informed consent for voluntary participation in the trial. Willing to undergo a baseline tumor core needle biopsy and blood draws for correlative science studies. Eighteen years of age or older on the day of signing informed consent. Female subjects must either be of non-reproductive potential or must have a negative urine or serum pregnancy test upon study entry. 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: Patients who underwent partial excisional biopsy or lumpectomy, segmental mastectomy or modified radical mastectomy or sentinel node. Patients for whom anthracycline, paclitaxel or antibody therapies are contraindicated. 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. Active or prior documented inflammatory bowel disease (Crohn's disease, ulcerative colitis). Patients with known active hepatitis B or C or HIV infection or with history of tuberculosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lajos Pusztai, MD, D. Phil.
Organizational Affiliation
Yale School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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