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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:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Neoadjuvant MEDI4736 Concomitant With Weekly <span class="go-doc-concept go-doc-intervention">Nab-paclitaxel</span> and Dose-dense AC for Stage I-III Triple Negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

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

    NCT ID: NCT02489448

    ORG ID: 1409014537

    Trial Conditions

    Breast Neoplasms

    Trial Interventions

    Drug Synonyms Arms
    MEDI4736 tremelimumab, anti-PD-L1 antibody MEDI4736

    Trial 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

    Name Type Description Interventions
    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. 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Pathologic Complete Response (pCR)

    Secondary Outcome Measures

    Trial Keywords

    Breast Cancer