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

NCT ID: NCT02520063

Last Updated: 2024-12-27

Study Results

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-02-23

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Letrozole

Intervention Type 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.

Everolimus

Intervention Type 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.

TRC105

Intervention Type 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 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

Group Type EXPERIMENTAL

Letrozole

Intervention Type 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.

Everolimus

Intervention Type 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.

TRC105

Intervention Type 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

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

Group Type EXPERIMENTAL

Letrozole

Intervention Type 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.

Everolimus

Intervention Type 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.

TRC105

Intervention Type 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 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.

Group Type EXPERIMENTAL

Letrozole

Intervention Type 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.

Everolimus

Intervention Type 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.

TRC105

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Femara Afinitor

Eligibility Criteria

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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

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Tracon Pharmaceuticals Inc.

INDUSTRY

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role lead

Responsible Party

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Christos Vaklavas, MD

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Erica Stringer-Reasor, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Erica Stringer-Reasor, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 36735117 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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F150701004 (UAB 1514)

Identifier Type: -

Identifier Source: org_study_id