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

NCT02520063 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: F150701004 (UAB 1514)UAB1514
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

hormone-receptor positive breast cancer; Her2 negative breast cancer; neoadjuvant; everolimus; TRC105; letrozole

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced Dose-limiting Toxicities

  This outcome will report the number of patients who experienced a dose-limiting Toxicity (DLT) in Phase I Cohort 1, Phase I Cohort 2, and Phase I Cohort -1. A DLT was defined as: 1. A grade 3 or 4 non-hematologic toxicity except anorexia, alopecia, nausea (which is not refractory to antiemetics), fatigue, and fever without neutropenia; 2. Failure to recover to baseline (except alopecia) after delaying the next dose by more than 14 days; 3. Grade 3 or 4 neutropenia complicated by fever \>38.5°C or infection, or grade 4 neutropenia of ≥7 days duration; or 4. Grade 4 thrombocytopenia, or grade 3 thrombocytopenia complicated by hemorrhage. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 out of the first 3 or 1 out of a total of 6 patients experience DLT during the first cycle of therapy; this dose level will be the recommended phase 2 dose (RP2D) in the Phase II Group.

  4 weeks

Secondary Outcomes (10)

• Rates of Pathologic Complete Remission (pCR)

  24 weeks up to time of surgery

• C Max - Letrozole

  Day 1 and Day 29

• Tumor Proliferation Changes

  24 weeks (pretreatment to time of definitive surgery)

• T Max - Letrozole

  Day 1

• AUC - Letrozole

  Day 1 and Day 29

Study Arms (4)

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

Drug: Letrozole; Drug: Everolimus; Drug: 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

Drug: Letrozole; Drug: Everolimus; Drug: 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

Drug: Letrozole; Drug: Everolimus; Drug: 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.

Drug: Letrozole; Drug: Everolimus; Drug: TRC105

Interventions

Letrozole DRUG

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.

Also known as: Femara

Phase I Cohort -1; Phase I Cohort 1; Phase I Cohort 2; Phase II

Everolimus DRUG

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.

Also known as: Afinitor

Phase I Cohort -1; Phase I Cohort 1; Phase I Cohort 2; Phase II

TRC105 DRUG

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.

Phase I Cohort -1; Phase I Cohort 1; Phase I Cohort 2; Phase II

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Novartis Pharmaceuticals: collaborator
• Tracon Pharmaceuticals Inc.: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

• Vaklavas C, Stringer-Reasor EM, Elkhanany AM, Ryan KJ, Li Y, Theuer CP, Acosta EP, Wei S, Yang ES, Grizzle WE, Forero-Torres A. A phase I/II study of preoperative letrozole, everolimus, and carotuximab in stage 2 and 3 hormone receptor-positive and Her2-negative breast cancer. Breast Cancer Res Treat. 2023 Apr;198(2):217-229. doi: 10.1007/s10549-023-06864-9. Epub 2023 Feb 3.

  PMID: 36735117 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Everolimus; carotuximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sirolimus; Macrolides; Lactones

Results Point of Contact

• Title: Erica Stringer-Reasor
• Organization: UAB

esreasor@uabmc.edu

2059759375

Study Officials

• Erica Stringer-Reasor, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Erica Stringer-Reasor, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 11, 2015
• Study Start: February 1, 2015
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: February 6, 2026
• Results First Posted: August 21, 2023

Record last verified: 2026-02

Locations

US (1)