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

NCT01231659 | Completed Phase 2 Results

• 1 other identifier: CRAD001JIL05
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Keywords

RAD001 (Everolimus); Letrozole; Breast cancer; Metastatic Breast cancer; Estrogen receptor positive; Failure of Tamoxifen; Anastrozole or Examestane

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Response Rate (ORR)

  Overall Response Rate (ORR) was defined as the proportion of patients whose best overall response was either complete response (CR) or partial response (PR) according to RECIST 1.0 for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions for a period of at least one month; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (ORR) = CR + PR. Only descriptive statistics.

  From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 15 months

Secondary Outcomes (4)

• Median Time to Progression-Free Survival (PFS)

  Date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to 66 months

• Median Time to Overall Survival (OS)

  From Date of randomization up to approximately 66 months

• Disease Control Rate (DCR)

  From the date of randomization until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 66 months

• Long-term Safety and Tolerability

  From Date of first dose up to approximately 66 months

Study Arms (1)

Everolimus + Letrozole

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Letrozole

Interventions

Everolimus DRUG

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

Also known as: RAD001

Everolimus + Letrozole

Letrozole DRUG

Letrozole 2.5 mg once daily

Everolimus + Letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Recurrence while on, or within 12 month of end of, adjuvant treatment with Tamoxifen , Anastrozole, or Exemestane.
• Recurrence while on, or within 24 month of end of, adjuvant treatment with Letrozole.
• Progression while on Tamoxifen, Anastrozole or Exemestane treatment for locally advanced or metastatic breast cancer.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Novartis Investigative Site

Jerusalem, 91120, Israel

Location

Novartis Investigative Site

Kfar Saba, 4428164, Israel

Location

Novartis Investigative Site

Petah Tikva, 49100, Israel

Location

Novartis Investigative Site

Ramat Gan, 52621, Israel

Location

Novartis Investigative Site

Rehovot, 76100, Israel

Location

Novartis Investigative Site

Tel Aviv, 62439, Israel

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2010
• First Posted: November 1, 2010
• Study Start: August 9, 2011
• Primary Completion: November 20, 2012
• Study Completion: April 30, 2017
• Last Updated: March 26, 2021
• Results First Posted: March 26, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

IL (7)