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

Primary Purpose

Metastatic Breast Cancer

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Sorafenib
Letrozole
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring breast cancer, Postmenopausal Women with Hormone Receptor-Positive Locally Advanced Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Georgetown University Hospital
  • Emory University
  • Rutgers Cancer Institute of New Jersey
  • Cooper Hospital/University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib and Letrozole

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Measure of Participants With Response and Progression Will be Evaluated 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.
Overall Survival (OS) as Assessed by the Number of Participants That Survived
From the start of treatment to the end of the study (three years) that participants are still alive. Measured by the meadian number.

Full Information

First Posted
March 5, 2008
Last Updated
May 3, 2023
Sponsor
Rutgers, The State University of New Jersey
Collaborators
Rutgers Cancer Institute of New Jersey, National Cancer Institute (NCI), Bayer, Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00634634
Brief Title
Phase I/II Trial of Letrozole and Sorafenib in Post-Menopausal Hormone-Receptor + Breast Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 11, 2008 (Actual)
Primary Completion Date
April 20, 2019 (Actual)
Study Completion Date
October 20, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
Rutgers Cancer Institute of New Jersey, National Cancer Institute (NCI), Bayer, Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
breast cancer, Postmenopausal Women with Hormone Receptor-Positive Locally Advanced Breast Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib and Letrozole
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Other Intervention Name(s)
Nexavar
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Letrozole
Other Intervention Name(s)
Femara
Intervention Description
Patients will take letrozole orally at a daily dose of 2.5 mg/day on Days 1 through 28
Primary Outcome Measure Information:
Title
Sorafenib in Combination With Fixed Dose of of 2.5mg of Letrozole Maximum Tolerated Dose (MTD)
Description
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.
Time Frame
twenty eight days
Secondary Outcome Measure Information:
Title
Measure of Participants With Response and Progression Will be Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines (Version 1.1) to Letrozole and Sorafenib
Description
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
Time Frame
6 months
Title
Median Progressive-Free Survival (PFS)
Description
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.
Time Frame
Three years
Title
Overall Survival (OS) as Assessed by the Number of Participants That Survived
Description
From the start of treatment to the end of the study (three years) that participants are still alive. Measured by the meadian number.
Time Frame
Three years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed invasive breast cancer Stage IIIB, IIIC with T4 lesion or Stage IV disease Breast cancer must be ER-positive and/or PR-positive Age ³ 18 years of age ECOG performance status 0, 1 or 2 Able to swallow and oral medication Adequate end organ function Written informed consent Exclusion Criteria: Prior hormonal therapy for metastatic disease Prior chemotherapy for metastatic disease Prior treatment with sorafenib Brain metastases or leptomeningeal disease Evidence or history of bleeding Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antoinette Tan, MD
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Cooper Hospital/University Medical Center
City
Voorhees
State/Province
New Jersey
ZIP/Postal Code
08690
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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