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

NCT02489448 | Completed Phase 1 Results DMC

• 1 other identifier: 1409014537
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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).

Conditions

Breast Neoplasms

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 26 weeks

Study Arms (1)

MEDI4736

EXPERIMENTAL

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

Interventions

MEDI4736 DRUG

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.

Also known as: tremelimumab, anti-PD-L1 antibody

MEDI4736

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale School of Medicine

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Lajos Pusztai, MD, DPhil Professor of Medicine (Medical Oncology)
• Organization: Yale School of Medicine

lajos.pusztai@yale.edu

(203) 737-8309

Study Officials

• Lajos Pusztai, MD, D. Phil.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2015
• First Posted: July 3, 2015
• Study Start: November 1, 2015
• Primary Completion: June 15, 2021
• Study Completion: August 2, 2021
• Last Updated: October 26, 2022
• Results First Posted: October 26, 2022

Record last verified: 2022-10

Locations

US (1)