Phase I/II Trial of Letrozole and Sorafenib in Post-Menopausal Hormone-Receptor + Breast Cancer

Phase 1

Completed

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: Sorafenib; Drug: Letrozole

• Registration Number: NCT00634634
• Lead Sponsor: Rutgers, The State University of New Jersey

Brief Summary

Letrozole is an aromatase inhibitor that is approved in the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. This phase I/II trial is studying the side effects and best dose of sorafenib when given in combination with letrozole and to see how well they work in treating postmenopausal women with metastatic breast cancer.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-03-05
• Study First Submitted QC: 2008-03-12
• Study First Posted: 2008-03-13
• Study Start: 2008-08-11
• Primary Completion: 2019-04-20
• Results First Submitted: 2022-10-08
• Study Completion: 2023-04-28
• Results First Submitted QC: 2023-05-03
• Results First Posted: 2023-05-06
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-17
• Last Update Posted: 2023-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 52

Inclusion Criteria

1. Histologically confirmed invasive breast cancer
2. Stage IIIB, IIIC with T4 lesion or Stage IV disease
3. Breast cancer must be ER-positive and/or PR-positive
4. Age ³ 18 years of age
5. ECOG performance status 0, 1 or 2
6. Able to swallow and oral medication
7. Adequate end organ function
8. Written informed consent

Exclusion Criteria

1. Prior hormonal therapy for metastatic disease
2. Prior chemotherapy for metastatic disease
3. Prior treatment with sorafenib
4. Brain metastases or leptomeningeal disease
5. Evidence or history of bleeding
6. Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Sorafenib and Letrozole	Sorafenib	-
Sorafenib and Letrozole	Letrozole	-

Primary Outcome Measures

Name	Time	Method
Sorafenib in Combination With Fixed Dose of of 2.5mg of Letrozole Maximum Tolerated Dose (MTD)	twenty eight days	The highest dose of the drug that does not cause unacceptable side effects. The maximum tolerated dose be testing increasing doses until the highest dose with acceptable side effects is found.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (Version 1.1) to Letrozole and Sorafenib	6 months	Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the malignant lymph nodes are used for tumor measurements. Included will be: complete response, partial response or stable disease of letrozole and sorafenib in the treatment of postmenopausal participants with hormone receptor- positive locally advanced or metastatic breast cancer.; Clinical Benefit Rate (CBR) = Progressive Free (PF) + Stable Disease (SD)
Median Progressive-Free Survival (PFS)	Approximately 4.6 years	PFS based on the Kaplan-Meier method is defined as the time between randomization and documented disease progression (PD) per RECIST 1,0 criteria or death, or is censored at time of last disease assessment. Per RECIST 1.0f or target lesions, PD is at least a 20% increase in sum LD of target lesions, taken as reference the smallest sum LD recorded at treatment started. Based on the time between the first day of treatment and and the date of disease progression.
Overall Survival (OS) Assessed as Mean Months	Approximately 4.6 years	From the start of treatment to the end of the study (three years) that participants are still alive. Measured by the mean number.

Trial Locations

Locations (4)

Emory University; 🇺🇸 Atlanta, Georgia, United States

Rutgers Cancer Institute of New Jersey; 🇺🇸 New Brunswick, New Jersey, United States

Cooper Hospital/University Medical Center; 🇺🇸 Voorhees, New Jersey, United States

Georgetown University Hospital; 🇺🇸 Washington, District of Columbia, United States