Overview

This trial is active, not recruiting.

Condition oestrogen receptor positive advanced breast cancer
Treatments rad001, exemestane
Phase phase 4
Targets mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date January 2013
End date June 2016
Trial size 50 participants
Trial identifier NCT01743560, 2012-003689-41, CRAD001YGB11

Summary

Determine the overall response rate (ORR) at 48 weeks to everolimus (RAD001, 10mg daily p.o.) and exemestane (25mg daily p.o.) treatment in postmenopausal women with oestrogen receptor positive breast cancer who have previous experienced recurrence or progression on non-steroidal aromatase inhibitor (NSAI) therapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Postmenopausal women diagnosed with oestrogen receptor positive locally advanced or metastatic breast cancer will receive RAD001 at a dose of 10mg daily p.o. and exemestane 25mg daily p.o. for 48 weeks.
rad001 Everolimus
All postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer will be treated with oral RAD001 at a dose of 10mg daily and oral exemestane 25mg daily. The study treatment for an individual patient will begin on Study Day 1 and will continue until the last patient enrolled has completed the study at day 336 or until disease progression; unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occurs first.
exemestane
All postmenopausal women with oestrogen receptor positive locally advanced or metastatic breast cancer will be treated with oral RAD001 at a dose of 10mg daily and oral exemestane 25mg daily. The study treatment for an individual patient will begin on Study Day 1 and will continue until the last patient enrolled has completed the study at day 336 or until disease progression; unacceptable toxicity, death or early discontinuation from the study for any other reason, whichever occurs first.

Primary Outcomes

Measure
Response rate of everolimus and exemestane treatment in postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer
time frame: 48 weeks

Secondary Outcomes

Measure
Progression Free Survival
time frame: Start of treatment to the date of event defined as first documented progression due to any cause up to 24 months
Overall Survival (OS)
time frame: Start of treatment to date of death due to any cause up to 36 months
Quality of life (EuroQol Standardised Health Outcome Questionnaire EQ-5D)
time frame: 48 weeks and 30 day follow up
Quality of life (EORTC Quality of Life Questionnaire of cancer patients QLQ-C30)
time frame: 48 weeks and 30 day follow up
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
time frame: Baseline to 48 Weeks and will be followed-up for 30 days after end of treatment for safety.

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Histological or cytological confirmation of oestrogen receptor positive (ER+) and/or progesterone receptor positive (PgR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer. - Availability of archival tumour tissue (the tissue block or slides will be sent to the central laboratory for analysis). - Postmenopausal women. The investigator must confirm postmenopausal status. Postmenopausal status is defined either by: - Age ≥ 55 years and one year or more of amenorrhea - Age < 55 years and one year or more of amenorrhea and postmenopausal levels of FSH and LH per local institutional standards - Prior hysterectomy and has postmenopausal levels of Follicle stimulating hormone (FSH) and Luteinizing Hormone (LH) per local institutional standards Surgical menopause with bilateral oophorectomy - Disease progression following prior therapy with NSAI, defined as: - Recurrence while on or after completion of an adjuvant treatment including letrozole or anastrozole, or - Progression while on or following the completion of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer Note: Non-steroidal aromatase inhibitors (i.e. letrozole or anastrozole) do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. tamoxifen, fulvestrant, exemestane are also allowed. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to enrollment. - Radiological evidence of recurrence or progression on last systemic therapy prior to enrollment. Patients must have: - At least one lesion that can be accurately measured or - Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease - Adequate bone marrow and coagulation function as shown by: - Absolute neutrophil count (ANC) ≥ 1.5 109/L - Platelets ≥ 100 ×109/L - Hemoglobin (Hb) ≥ 9.0 g/dL - International Normalized Ratio (INR) ≤ 2 . - Adequate liver function as shown by: - Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN (or ≤ 5 if hepatic metastases are present) - Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients known to have Gilbert Syndrome) - Adequate renal function as shown by: - Serum creatinine ≤ 1.5 × ULN - Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy and when the above mentioned values have been achieved - Eastern Cooperative Oncology Group (ECOG) performance status of PS 1.5 × ULN - Acute and chronic, active infectious disorders (except for Hep B and Hep C positive patients) and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy - Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome) - Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates. - Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (rifabutin, rifampicin, clarithromycin, ketoconazole, itraconazole, voriconazole, ritonavir, telithromycin) within the last 5 days prior to enrollment - History of non-compliance to medical regimens - Patients unwilling to or unable to comply with the protocol - Another malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer

Additional Information

Official title A Phase IV Multicentre, Open Label Study of Postmenopausal Women With Oestrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer Treated With Everolimus (RAD001) in Combination With Exemestane, With Exploratory Epigenetic Marker Analysis
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Novartis.