Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT01231659

Last Updated: 2021-03-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-09
• Study Completion Date: 2017-04-30

Brief Summary

This was a multi-center, Israeli phase II open label study evaluating treatment with RAD001 (10 mg daily) combined with letrozole (2.5 mg daily) in postmenopausal women after recurrence or progression on Tamoxifen, Anastrozole or Examestane.

There were no treatments specifically approved after recurrence or progression on AIs. Available options, based on common clinical practice and several treatment guidelines (e.g. NCCN treatment guidelines 2008), included fulvestrant.

Combining RAD001 with letrazole was a rational approach to the treatment of advanced Brest Cancer, offering the potential for inhibition of tumor cell growth\ proliferation and anti angiogenesis while at the same time potentially preventing the development of letrazole resistance.

Detailed Description

Screening Period:

Postmenopausal women with estrogen receptor positive, locally advanced or metastatic breast cancer whose disease was refractory to hormonal therapy and had a documented recurrence or progression on last therapy for their breast cancer with either tamoxifen, anastrozole, letrozole, fulvestrant or exemestan were screened for eligibility within 28 days prior to treatment Day 1.

Treatment Period:

Patients started receiving everolimus (10 mg daily oral dose) combined with letrozole (2.5 mg daily oral dose) tablets from treatment Day 1. Study treatment continued until disease progression, intolerable toxicity or consent withdrawal. Dose adjustment (reduction, interruption or possible dose re-escalation to starting dose) could be done based on the safety findings. Tumor assessments were performed every 12 weeks until disease progression. In order to confirm response at least four weeks after first observation, additional scans to determine a complete response (CR) or partial response (PR) or stable disease (SD) were performed. Patients were followed for safety until 28 days after study treatment discontinuation.

Post Treatment Follow up for Survival:

Patients were followed for survival every 3 months for up to 3 years. Survival information could be obtained via phone and information was documented in the source documents.

Conditions

Postmenopausal Women; Locally Advanced Metastatic Breast Cancer; Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus + Letrozole

All patients received 2 tablets (5 mg each) of Everolimus (a total of 10 mg) + 1 tablet of Letrozole (2.5 mg) daily until disease progression or as described in the protocol.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Everolimus 10 mg (2 tablets of 5 mg) once daily

Letrozole

Intervention Type: DRUG

Letrozole 2.5 mg once daily

Interventions

Everolimus

Everolimus 10 mg (2 tablets of 5 mg) once daily

Intervention Type: DRUG

Letrozole

Letrozole 2.5 mg once daily

Intervention Type: DRUG

Other Intervention Names

RAD001

Eligibility Criteria

Inclusion Criteria

• Postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer after documented recurrence or progression on Tamoxifen, Anastrozole or Examestane.

• Refractory disease to hormonal therapy is defined as:

1. Recurrence while on, or within 12 month of end of, adjuvant treatment with Tamoxifen , Anastrozole, or Exemestane.

2. Recurrence while on, or within 24 month of end of, adjuvant treatment with Letrozole.

3. Progression while on Tamoxifen, Anastrozole or Exemestane treatment for locally advanced or metastatic breast cancer.

Exclusion Criteria

• Prior use of chemotherapy and letrozole for Advanced Breast Cancer and mTOR inhibitors as the last anticancer treatment prior to study entry.
• Patients must have radiological evidence of recurrence or progression on last therapy prior to study entry.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Jerusalem, , Israel

Novartis Investigative Site

Kfar Saba, , Israel

Novartis Investigative Site

Petah Tikva, , Israel

Novartis Investigative Site

Ramat Gan, , Israel

Novartis Investigative Site

Rehovot, , Israel

Novartis Investigative Site

Tel Aviv, , Israel

Novartis Investigative Site

Tel Aviv, , Israel

Countries

Israel

Other Identifiers

CRAD001JIL05

Identifier Type: -

Identifier Source: org_study_id