Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole - Full Text View

Sponsor:	Novartis Pharmaceuticals
Information provided by (Responsible Party):	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00863655

Purpose

There are no treatments specifically approved after recurrence or progression on a NSAI. In light of the need for new treatment options for postmenopausal women after failure of prior non steroidal aromatase inhibitors (NSAI) therapy, the purpose of this Phase III study is to compare efficacy and safety of a treatment with exemestane + everolimus to exemestane + placebo in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAI.

Condition	Intervention	Phase
Breast Cancer	Drug: Everolimus, Exemestane Drug: Placebo, Exemestane	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination With Exemestane in the Treatment of Postmenopausal Women With Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Who Are Refractory to Letrozole or Anastrozole

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Sirolimus Exemestane Letrozole Anastrozole Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Progression-free survival (PFS) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
PFS is defined as the time from the date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first.

Secondary Outcome Measures:

Overall survival (OS) [ Time Frame: Every 3 months after End of Treatment + 28 days (every 6 weeks before) ] [ Designated as safety issue: No ]
Overall survival, the key secondary endpoint in this study, is defined as the time from date of randomization to the date of death due to any cause.
Overall response rate (ORR) [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
ORR is defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST.
Incidence of adverse events (AEs)/serious adverse events (SAEs) [ Time Frame: Continuous and every 6 weeks ] [ Designated as safety issue: Yes ]
In addition to AEs/SAEs, shift from baseline in vital signs and laboratory results (hematology, blood chemistry) will be reported.
Patient reported outcome (PRO). [ Time Frame: Every 6 weeks ] [ Designated as safety issue: Yes ]
Clinical benefit rate (CBR) [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
CBR is defined as the proportion of patients whose best overall response is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks, according to RECIST.

Estimated Enrollment:	724
Study Start Date:	June 2009
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Everolimus + Exemestane Everolimus 10 mg daily in combination with exemestane 25 mg daily	Drug: Everolimus, Exemestane Other Name: RAD001
Active Comparator: Placebo + Exemestane Placebo of everolimus in combination with exemestane 25 mg daily	Drug: Placebo, Exemestane

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
Postmenopausal women.
Disease refractory to non steroidal aromatase inhibitors (NSAI),
Radiological or clinical evidence of recurrence or progression on or after the last systemic therapy prior to randomization.
Patients must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease as defined above.

Exclusion Criteria:

HER2-overexpressing patients
Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites etc.).
Patients who received more than one chemotherapy line for Advanced Breast Cancer.
Previous treatment with exemestane or mTOR inhibitors.
Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
Radiotherapy within four weeks prior to randomization
Currently receiving hormone replacement therapy, Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00863655

Show 205 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:	Novartis Pharmaceuticals	Novartis Pharmaceuticals
Study Director:	Novartis Pharmaceuticlas	Novartis Pharmaceuticals

More Information

Additional Information:

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Baselga J, Campone M, Piccart M, Burris HA 3rd, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, Beck JT, Ito Y, Yardley D, Deleu I, Perez A, Bachelot T, Vittori L, Xu Z, Mukhopadhyay P, Lebwohl D, Hortobagyi GN. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012 Feb 9;366(6):520-9. Epub 2011 Dec 7.

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT00863655 History of Changes
Other Study ID Numbers:	CRAD001Y2301, 2008-008698-69
Study First Received:	March 16, 2009
Last Updated:	May 4, 2012
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Austria: Agency for Health and Food Safety Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Brazil: National Health Surveillance Agency Canada: Health Canada Czech Republic: State Institute for Drug Control Egypt: Ministry of Health, Drug Policy and Planning Center France: Afssaps - French Health Products Safety Agency Germany: Federal Institute for Drugs and Medical Devices Hong Kong: Department of Health Hungary: National Institute of Pharmacy Italy: National Institute of Health Japan: Pharmaceuticals and Medical Devices Agency Netherlands: Medicines Evaluation Board (MEB) New Zealand: Food Safety Authority Norway: Norwegian Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products South Korea: Korea Food and Drug Administration (KFDA) Spain: Spanish Agency of Medicines Sweden: Medical Products Agency Thailand: Food and Drug Administration Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:

Breast Cancer
Estrogen Receptor positive
ER+
exemestane

mTOR
everolimus
refractory
NSAI

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Exemestane
Letrozole
Anastrozole
Sirolimus
Everolimus
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on May 23, 2012