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

Metastatic Breast Cancer Clinical Trial

Official title:

Phase I/II Trial of Letrozole (Femara) and Sorafenib (Nexavar) in Postmenopausal Women With Hormone-Receptor Positive Locally Advanced or Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00634634
• Other study ID #: 040706
• Secondary ID: NJ 1107022007028
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 11, 2008
• Est. completion date: April 28, 2023

Study information

• Verified date: October 2023
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: April 28, 2023
• Est. primary completion date: April 20, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Sorafenib
sorafenib dose will be given at a daily dose to be determined based upon the phase of study that patient is enrolled The phase II dose of sorafenib will be determined from the phase I portion of the study.
• Letrozole
Patients will take letrozole orally at a daily dose of 2.5 mg/day on Days 1 through 28

Locations

Country	Name	City	State
United States	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

Sponsors (5)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey	Bayer, National Cancer Institute (NCI), Novartis Pharmaceuticals, Rutgers Cancer Institute of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sorafenib in Combination With Fixed Dose of of 2.5mg of Letrozole Maximum Tolerated Dose (MTD)	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.	twenty eight days
Secondary	Clinical Benefit Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (Version 1.1) to Letrozole and Sorafenib	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)	6 months
Secondary	Median Progressive-Free Survival (PFS)	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.	Approximately 4.6 years
Secondary	Overall Survival (OS) Assessed as Mean Months	From the start of treatment to the end of the study (three years) that participants are still alive. Measured by the mean number.	Approximately 4.6 years