Letrozole + Everolimus + TRC105 for Breast Cancer

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Alabama at Birmingham

Disqualifiers: Inflammatory breast cancer, Pregnancy, Metastatic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 105

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using three drugs together to treat a specific type of breast cancer in postmenopausal women before surgery. The drugs work by blocking hormones, growth signals, and blood supply to the tumor. The trial involves the use of advanced medications that have been introduced as effective treatments for postmenopausal women with this type of breast cancer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Letrozole, Everolimus, and TRC105 for breast cancer?

Research shows that combining everolimus with letrozole can improve progression-free survival (the time during which the cancer does not get worse) in patients with hormone receptor-positive, HER2-negative advanced breast cancer. This suggests that using these drugs together can be an effective treatment option. ^{1 2 3 4 5}

Is the combination of Letrozole, Everolimus, and TRC105 generally safe for humans?

Everolimus, when combined with other treatments like exemestane or letrozole, has been shown to have an acceptable safety profile in patients with advanced breast cancer, with side effects that are manageable. The safety of Everolimus in combination with Letrozole has been studied, but specific safety data for the combination with TRC105 is not provided in the available research. ^{1 2 6 7 8}

What makes the drug combination of Letrozole, Everolimus, and TRC105 unique for breast cancer treatment?

This drug combination is unique because it combines Letrozole, an aromatase inhibitor that reduces estrogen production, with Everolimus, which blocks a protein called mTOR involved in cancer cell growth, and TRC105, which targets blood vessels that supply tumors, potentially offering a more comprehensive approach to treating hormone receptor-positive, HER2-negative breast cancer. ^{1 2 3 4 7}

Research Team

Erica Stringer-Reasor, M.D.

Principal Investigator

University of Alabama at Birmingham

Erica Stringer-Reasor, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for postmenopausal women with Stage 2 or 3 hormone receptor-positive and HER2-negative breast cancer, who haven't had treatment for it yet. They should be relatively healthy (ECOG < 2), have good blood counts and liver/renal function, and must consent to the study.

Inclusion Criteria

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

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

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

Exclusion Criteria

Metastatic disease.

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

Disease that cannot be followed by imaging studies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Determine the ideal combination of doses of Letrozole, Everolimus, and TRC105 for tolerance

4 weeks

Regular visits for dose-limiting toxicity assessment

Phase II Treatment

Participants receive the investigational combination of Letrozole, Everolimus, and TRC105 to assess preliminary efficacy

24 weeks

Bi-weekly visits for TRC105 administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Everolimus
• Letrozole
• TRC105

Trial Overview The trial tests a new drug combo: Letrozole (blocks estrogen receptors), Everolimus (stops cancer growth signals), and TRC105 (prevents blood vessel growth in tumors). It aims to see if this mix can safely improve outcomes before surgery.

Participant Groups

Group I: Phase II Experimental Treatment 3 Interventions

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 II: Phase I Cohort 2 Experimental Treatment 3 Interventions

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 III: Phase I Cohort 1 Experimental Treatment 3 Interventions

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 IV: Phase I Cohort -1 Experimental Treatment 3 Interventions

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

Everolimus is already approved in United States, European Union for the following indications:

Approved in United States as Afinitor for:

• Advanced renal cell carcinoma
• Subependymal giant cell astrocytoma
• Progressive neuroendocrine tumors of pancreatic origin
• Advanced hormone receptor-positive, HER2-negative breast cancer
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in European Union as Votubia for:

• Subependymal giant cell astrocytoma
• Renal angiomyolipoma
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in United States as Zortress for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Tracon Pharmaceuticals Inc.

Industry Sponsor

Trials

22

Recruited

1,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

References

1. United States pubmed.ncbi.nlm.nih.gov

Everolimus Plus Letrozole for Treatment of Patients With HR+, HER2- Advanced Breast Cancer Progressing on Endocrine Therapy: An Open-label, Phase II Trial. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Leuprorelin combined with letrozole with/without everolimus in ovarian-suppressed premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer: The LEO study. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Everolimus Boosts Endocrine Therapy for Breast Cancer. [2018]

6. Belgium pubmed.ncbi.nlm.nih.gov

[The drug of the month: everolimus (Afinitor) for the treatment of metastatic breast cancer]. [2015]

7. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of everolimus combined with endocrine therapy in HR-positive/HER-2-negativeadvanced breast cancer. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer. [2020]