Overview

This trial is active, not recruiting.

Condition breast cancer
Treatments capecitabine, exemestane, everolimus
Phase phase 2
Targets mTOR, FKBP-12
Sponsor Novartis Pharmaceuticals
Start date February 2013
End date October 2017
Trial size 322 participants
Trial identifier NCT01783444, CRAD001Y2201

Summary

This study will assess the efficacy and tolerability of everolimus and capecitabine monotherapies compared to everolimus/exemestane combination in woman with ER + advanced breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
100 patients will be randomized to the Capecitabine monotherapy arm (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles.
capecitabine Capecitabine monotherapy
Capecitabine, for oral use 1250 mg/m2 twice daily for 2 weeks followed by one week rest (3-week cycle). Capecitabine will be locally supplied by the Investigator.
(Experimental)
100 patients will be randomized to this arm and will received Everolimus (10mg daily).
everolimus RAD001
Everolimus will be centrally dispensed via IWRS. Everolimus will be taken as oral tablets for oral use 10 mg (2 × 5 mg) daily.
(Active Comparator)
100 patients will be randomized to the control arm of this study, everolimus (10mg daily) with exemestane (25mg daily).
exemestane Control Arm
Exemestane tablets of 25 mg will be taken orally once per day. Dose modifications in the management of adverse events is allowed.

Primary Outcomes

Measure
Progression Free Survival (PFS)
time frame: 28 months after first patient randomized or once 150 PFS have occurred

Secondary Outcomes

Measure
Overall Survival
time frame: Every 3 months following the end of study visit until 2015 (up to 3 years)
Overall response rate
time frame: From the date of first dose of study medication until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately for 28 months
Clinical benefit rate (CBR)
time frame: From the date of first dose of study medication until the date of the first documented disease progression or date of death from any cause whichever came first, assessed for approximately 28 months
Changes in ECOG (Eastern Cooperative Oncology Group) performance status
time frame: Baseline, Day 1, every 6 weeks for approximately 8 months
Change in quality of life scores over time: EORTC (QLQ-C30)/EORTC module (BR23)
time frame: Baseline, every 6 weeks for approximately 8 months
Time to quality of life (QoL)deterioration : TSQM score
time frame: Baseline, week 3,6, 12 for approximately 8 months
Safety: Incidence of Adverse Event(s)
time frame: every study visit for approximately 8 months
Safety: Incidence of Serious Adverse Events
time frame: every study visit for approximately 8 months
Safety: changes in vital signs when compared to baseline vital signs
time frame: baseline, every study visit for approximately 8 months
Safety: changes in laboratory values compared to laboratory values obtained at the baseline visit
time frame: baseline, every study visit for approximately 8 months

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: -Women with locally advanced, recurrent, or metastatic breast cancer along with confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least one lesion ≥ 10 mm by CT or MRI that can be accurately measured in at least one dimension (CT scan slice thickness ≤ 5 mm) OR • Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above Exclusion Criteria: -Patients who received more than one chemotherapy line. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors Other protocol-defined inclusion/exclusion criteria may apply.

Additional Information

Official title Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in the Treatment of Postmenopausal Women With ER+Locally Advanced, Recurrent, or Metastatic Breast Cancer After Recurrence or Progression on Prior Letrozole or Anastrozole.
Description This is a three-arm, randomized, open label, multi-center phase II study investigating the combination of everolimus (10mg daily) with exemestane (25mg daily) versus everolimus (10mg daily) versus capecitabine (1250mg/m2 twice daily for 14 days, 3-week cycle) in patients with estrogen-receptor positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole. The reference therapy (control arm) used in the course of this trial is the combination arm of everolimus plus exemestane. The investigational therapies in the context of this study are everolimus monotherapy and capecitabine monotherapy. All treatments will be taken orally until disease progression, intolerable toxicity or withdrawal of patient's informed consent. Patients will be randomly assigned with equal allocation to one of the treatment arms: 1. Exemestane (25mg daily) in combination with everolimus (10mg daily) 2. Everolimus (10mg daily) 3. Capecitabine (1250mg/m2 twice daily) orally for two weeks, followed by a one week rest period in 3-weeks cycles. Treatment assignment will be stratified by the presence of visceral disease (yes vs. no). Visceral refers to lung, liver, heart, ovary, spleen, kidney, adrenal gland, malignant pleural or pericardial effusion or malignant ascites.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Novartis.