Clinical Trials /

Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer

NCT02520063

Description:

This study will test how well a new combination of three drugs (Letrozole, Everolimus, and TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an investigational drug that blocks the formation and growth of blood vessels that feed the cancer and promote its growth. The goal of this study is to investigate the safety and efficacy of this multitargeted approach in breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Preoperative Combination of <span class="go-doc-concept go-doc-intervention">Letrozole</span>, <span class="go-doc-concept go-doc-intervention">Everolimus</span>, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer
  • Official Title: A Phase I/II Study of Preoperative (Neoadjuvant) Combination of Letrozole (Femara), Everolimus (Afinitor), and TRC105 in Postmenopausal Women With Newly Diagnosed Local or Locally Advanced Potentially Resectable Hormone-Receptor Positive and Her2 Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02520063

    ORG ID: UAB 1514

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Letrozole Femara Phase I Cohort 1, Phase I Cohort 2, Phase I Cohort -1, Phase II
    Everolimus Afinitor Phase I Cohort 1, Phase I Cohort 2, Phase I Cohort -1, Phase II
    TRC105 Phase I Cohort 1, Phase I Cohort 2, Phase I Cohort -1, Phase II

    Trial Purpose

    This study will test how well a new combination of three drugs (Letrozole, Everolimus, and
    TRC105) is tolerated and how well it works in Stage 2 and 3 breast cancer when given prior
    to definitive surgery. Letrozole blocks the estrogen receptor expressed by many breast
    cancers while everolimus blocks signals that drive cancer cells to grow. TRC105 is an
    investigational drug that blocks the formation and growth of blood vessels that feed the
    cancer and promote its growth. The goal of this study is to investigate the safety and
    efficacy of this multitargeted approach in breast cancer.

    Detailed Description

    In postmenopausal women with hormone receptor-positive and Her2 negative non-metastatic
    breast cancer, downstaging or the achievement of a complete pathologic remission before
    definitive surgery has been associated with the lowest risk of recurrence of breast cancer.
    In order to achieve a better response in these patients in the preoperative setting, this
    study combines 3 potentially synergistic agents. Letrozole blocks the synthesis of estrogens
    and, in doing so, deprives the tumor from hormones which drive its growth. Everolimus is a
    drug that blocks growth factor signaling which is essential for tumor cells to maintain
    their growth and proliferation. Everolimus has already been shown to work very well in this
    subtype of breast cancer in the recurrent and metastatic setting. TRC105 is an
    investigational agent that prevents the formation and growth of new blood vessels that
    support tumors by providing oxygen and nutrients.

    The study has 2 components. First the investigators will determine the ideal in terms of
    tolerance combination of doses of the 3 agents. Once the ideal regimen is determined, more
    patients will be treated with the investigational combination. During this second stage, the
    investigators will get a preliminary idea of how effective the investigational therapy is.
    Further studies will need to be done to confirm the efficacy of the investigational
    combination.

    Trial Arms

    Name Type Description Interventions
    Phase I Cohort 1 Experimental Letrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks Letrozole, Everolimus, TRC105
    Phase I Cohort 2 Experimental Letrozole 2.5 mg PO daily until surgery, everolimus 10 mg PO daily for 24 weeks, and TRC105 15 mg/kg IV q 2 weeks for 24 weeks Letrozole, Everolimus, TRC105
    Phase I Cohort -1 Experimental Letrozole 2.5 mg PO daily until surgery, everolimus 5 mg PO daily for 24 weeks, and TRC105 10 mg/kg IV q 2 weeks for 24 weeks Letrozole, Everolimus, TRC105
    Phase II Experimental Letrozole 2.5 mg PO daily until surgery, everolimus 5 or 10 mg PO daily for 24 weeks, and TRC105 15 or 10 mg/kg IV q 2 weeks for 24 weeks. Dose and regimen to be determined based on data from the phase I component. Letrozole, Everolimus, TRC105

    Eligibility Criteria

    Inclusion Criteria:

    - Recent diagnosis of hormone receptor positive and HER2 negative breast cancer.

    - Stage 2 and 3 hormone receptor positive and HER2 negative breast cancer (stage T2-4
    but not inflammatory, N0-2, M0).

    - Histological grade I, II or III according to the modified Bloom Richardson scale.

    - No prior treatment specific for breast cancer.

    - Postmenopausal status as defined by the National Comprehensive Cancer Network.

    - ECOG performance status < 2 (Karnofsky > 60%).

    - Must have signed study-specific informed consent.

    - Liver Function Tests < 2.5 times the upper normal limit (UNL).

    - ANC 1,500/mm3, platelets 100,000/mm3, Hemoglobin 10g%.

    - Renal function: serum creatinine < 1.5 institutional UNL or creatinine clearance > 40
    cc/min.

    Exclusion Criteria:

    - Inflammatory breast cancer.

    - Pre- and peri-menopausal state.

    - Pregnancy.

    - Metastatic disease.

    - HER2 positive breast cancer by immunohistochemistry or FISH.

    - Triple negative breast cancer (hormone receptor and Her2 negative).

    - Disease that cannot be followed by imaging studies.

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Maximum tolerated dose (MTD)

    Secondary Outcome Measures

    Rates of pathologic complete remission (pCR)

    C max

    Tumor proliferation changes

    T max

    AUC

    T 1/2

    Trial Keywords

    hormone-receptor positive breast cancer

    Her2 negative breast cancer

    neoadjuvant

    everolimus

    TRC105

    letrozole