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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Sorafenib; Drug: Letrozole

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
    • Voorhees, New Jersey, United States, 08690
      • Cooper Hospital/University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib and Letrozole	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.; Other Names: Nexavar; Drug: Letrozole; Patients will take letrozole orally at a daily dose of 2.5 mg/day on Days 1 through 28; Other Names: Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Rutgers, The State University of New Jersey
• Collaborators: National Cancer Institute (NCI); Bayer; Novartis Pharmaceuticals; Rutgers Cancer Institute of New Jersey
• Investigators: Principal Investigator: Antoinette Tan, MD, Rutgers Cancer Institute of New Jersey

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2008
• Primary Completion (Actual): April 20, 2019
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: March 5, 2008
• First Submitted That Met QC Criteria: March 12, 2008
• First Posted (Estimated): March 13, 2008

Study Record Updates

• Last Update Posted (Estimated): November 9, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; Postmenopausal Women with Hormone Receptor-Positive Locally Advanced Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Sorafenib; Letrozole
• Other Study ID Numbers: 040706 (Rutgers Cancer Institute of New Jersey); NJ 1107 (Other Identifier: CINJOG); 0220070284 (Other Identifier: Rutgers Cancer Institute of New Jersey); NCI-2012-00525 (Other Identifier: NCI #); Pro2018001861 (Other Identifier: Rutgers IRB#)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO