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Trial record 1 of 1 for:    NCT02520063
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Preoperative Combination of Letrozole, Everolimus, and TRC105 in Postmenopausal Hormone-Receptor Positive and Her2 Negative Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2016 by University of Alabama at Birmingham
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Tracon Pharmaceuticals Inc.
Information provided by (Responsible Party):
Christos Vaklavas, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT02520063
First received: July 30, 2015
Last updated: December 22, 2016
Last verified: December 2016
  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.

Condition Intervention Phase
Breast Cancer
Drug: Letrozole
Drug: Everolimus
Drug: TRC105
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) [ Time Frame: 4 weeks ]
    The highest dose at which 0 out of the first 3 or 1 out of a total of 6 patients experience dose limiting toxicity associated with the combination of letrozole with everolimus and TRC105 during the first cycle of therapy.


Secondary Outcome Measures:
  • Rates of pathologic complete remission (pCR) [ Time Frame: 24 weeks up to time of surgery ]
    The 2-dimensional size of the surgically excised residual tumor will be measure and compared to the radiographic size of the tumor at baseline.

  • C max [ Time Frame: collections over 24 hours on Day 1 and Day 25 ]
    Maximum serum concentration of the interaction between TRC105 and everolimus

  • Tumor proliferation changes [ Time Frame: 24 weeks up to time of surgery ]
    Determine the changes in tumor cell proliferation by means of changes in Ki67 expression and changes in serum concentration of markers of angiogenesis

  • T max [ Time Frame: collections over 24 hours on Day 1 and Day 25 ]
    Time of maximum serum concentration of the interaction between TRC105 and everolimus

  • AUC [ Time Frame: collections over 24 hours on Day 1 and Day 25 ]
    Area under the serum concentration versus time curve

  • T 1/2 [ Time Frame: collections over 24 hours on Day 1 and Day 25 ]
    Terminal half-life of the interaction between TRC105 and everolimus


Estimated Enrollment: 35
Study Start Date: February 2016
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I Cohort 1
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
Drug: Letrozole
A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Other Name: Femara
Drug: Everolimus
The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
Other Name: Afinitor
Drug: TRC105
The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery.
Experimental: Phase I Cohort 2
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
Drug: Letrozole
A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Other Name: Femara
Drug: Everolimus
The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
Other Name: Afinitor
Drug: TRC105
The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery.
Experimental: Phase I Cohort -1
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
Drug: Letrozole
A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Other Name: Femara
Drug: Everolimus
The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
Other Name: Afinitor
Drug: TRC105
The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery.
Experimental: Phase II
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.
Drug: Letrozole
A dose of 2.5 mg of letrozole will be given orally once each day until one day before surgery. This drug is commercially available and is not provided by the study.
Other Name: Femara
Drug: Everolimus
The dose of everolimus will be escalated from 5 mg to 10 mg daily depending upon the cohort in Phase I. It is administered as an oral pill to be taken once daily up until four weeks prior to surgery.
Other Name: Afinitor
Drug: TRC105
The dose for TRC105 is either 15 or 10 mg/kg to be given intravenously every two weeks and continued until four weeks prior to surgery.

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.

  Eligibility

Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  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: NCT02520063

Contacts
Contact: Christos Vaklavas, M.D. 205-934-5677 cvaklavas@uabmc.edu

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Christos Vaklavas, M.D.    205-934-5677    cvaklavas@uabmc.edu   
Principal Investigator: Christos Vaklavas, M.D.         
Principal Investigator: Andres Forero-Torres, M.D.         
Sponsors and Collaborators
University of Alabama at Birmingham
Novartis Pharmaceuticals
Tracon Pharmaceuticals Inc.
Investigators
Principal Investigator: Christos Vaklavas, M.D. University of Alabama at Birmingham
Principal Investigator: Andres Forero-Torres, M.D. University of Alabama at Birmingham
  More Information

Responsible Party: Christos Vaklavas, MD, Assistant Professor, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02520063     History of Changes
Other Study ID Numbers: F150701004 (UAB 1514)
Study First Received: July 30, 2015
Last Updated: December 22, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by University of Alabama at Birmingham:
hormone-receptor positive breast cancer
Her2 negative breast cancer
neoadjuvant
everolimus
TRC105
letrozole

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Hormones
Letrozole
Everolimus
Sirolimus
Antibodies, Monoclonal
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on March 24, 2017