Safety and Efficacy of RAD001 (Everolimus) in Combination With Letrozole in the Treatment of Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer (MACS1016)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01231659
First received: October 28, 2010
Last updated: December 1, 2013
Last verified: December 2013
  Purpose

This is 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 are 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), include fulvestrant.

Combining RAD001 with letrazole is 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.


Condition Intervention Phase
Postmenopausal Women,
Locally Advanced or Metastatic Breast Cancer
Drug: Everolimus + Letrozole
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Open Label Study of Everolimus (RAD001) in Combination With Letrozole in the Treatment of Post Menopausal Women With Locally Advanced or Metastatic Breast Cancer Women With Estrogen Receptor Positive After Failure of Tamoxifen and or Anestrozole or Examestane.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: until 1st progression ] [ Designated as safety issue: No ]
    imaging every 12 weeks


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: until 1st progression ] [ Designated as safety issue: No ]
    imaging every 12 weeks

  • Overall Survival (OS) [ Time Frame: 3 years after LPLV ] [ Designated as safety issue: No ]
    by phone call to the patient

  • Disease Control Rate (DCR) [ Time Frame: until disease progression ] [ Designated as safety issue: No ]
    imaging every 12 weeks

  • Characterize the safety profile [ Time Frame: All study duration ] [ Designated as safety issue: Yes ]
    Adverse Events Serious Adverse Events, abs, ECG


Enrollment: 73
Study Start Date: August 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus + Letrozole
Everolimus 10 mg + Letrozole 2.5 mg
Drug: Everolimus + Letrozole
Other Name: RAD001

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  • Other protocol-defined inclusion/exclusion criteria may apply.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01231659

Locations
Israel
Novartis Investigative Site
Jerusalem, Israel, 91120
Novartis Investigative Site
Kfar-Sava, Israel, 44281
Novartis Investigative Site
Petach Tikva, Israel, 49100
Novartis Investigative Site
Ramat Gan, Israel, 52621
Novartis Investigative Site
Rehovot, Israel, 76100
Novartis Investigative Site
Tel-Aviv, Israel, 64239
Novartis Investigative Site
Zrifin, Israel, 70300
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01231659     History of Changes
Other Study ID Numbers: CRAD001JIL05
Study First Received: October 28, 2010
Last Updated: December 1, 2013
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

Keywords provided by Novartis:
RAD001 (Everolimus)
Letrozole
Breast cancer
Metastatic Breast cancer
Estrogen receptor positive
Failure of Tamoxifen
Anastrozole or Examestane

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Everolimus
Sirolimus
Letrozole
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014