A Phase II Study of Everolimus in Combination With Exemestane Versus Everolimus Alone Versus Capecitabine in Advance Breast Cancer. (BOLERO-6)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01783444
First received: January 11, 2013
Last updated: June 18, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Capecitabine
Drug: Exemestane
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 28 months after first patient randomized or once 150 PFS have occurred ] [ Designated as safety issue: No ]
    Once 150 PFS events have occured (determined by local assessment). To estimate the hazard ratio of PFS for everolimus plus exemestane versus everolimus alone in postmenopausal women with ER positive, HER2 negative, advanced breast cancer after recurrence or progression on letrozole or anastrozole.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Every 3 months following the end of study visit until 2015 (up to 3 years) ] [ Designated as safety issue: No ]
    To evaluate the treatment groups with respect to Overall Survival. End of study visit is defined as time when progression of disease recorded or death whichever comes first.

  • 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 ] [ Designated as safety issue: No ]
    Overall response rate (ORR) based on the local radiologist/investigator's tumor assessment (RECIST 1.1)

  • 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 ] [ Designated as safety issue: No ]
    Clinical Benefit Rate is defined as the proportion of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD) with duration of 24 weeks or longer.

  • Changes in ECOG (Eastern Cooperative Oncology Group) performance status [ Time Frame: Baseline, Day 1, every 6 weeks for approximately 8 months ] [ Designated as safety issue: No ]
    The ECOG performance status scale (1-5) allows patients to be classified as to their functional impairment, ECOG performance status will be compared to baseline ECOG performance classification.

  • Change in quality of life scores over time: EORTC (QLQ-C30)/EORTC module (BR23) [ Time Frame: Baseline, every 6 weeks for approximately 8 months ] [ Designated as safety issue: No ]
  • Time to quality of life (QoL)deterioration : TSQM score [ Time Frame: Baseline, week 3,6, 12 for approximately 8 months ] [ Designated as safety issue: No ]
  • Safety: Incidence of Adverse Event(s) [ Time Frame: every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of Serious Adverse Events [ Time Frame: every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]
  • Safety: changes in vital signs when compared to baseline vital signs [ Time Frame: baseline, every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]
  • Safety: changes in laboratory values compared to laboratory values obtained at the baseline visit [ Time Frame: baseline, every study visit for approximately 8 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 300
Study Start Date: February 2013
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Capecitabine Monotherapy
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.
Drug: Capecitabine
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.
Other Name: Capecitabine monotherapy
Experimental: Everolimus Monotherapy
100 patients will be randomized to this arm and will received Everolimus (10mg daily).
Drug: Everolimus
Everolimus will be centrally dispensed via IWRS. Everolimus will be taken as oral tablets for oral use 10 mg (2 × 5 mg) daily.
Other Name: RAD001
Active Comparator: Everolimus with Exemestane
100 patients will be randomized to the control arm of this study, everolimus (10mg daily) with exemestane (25mg daily).
Drug: Exemestane
Exemestane tablets of 25 mg will be taken orally once per day. Dose modifications in the management of adverse events is allowed.
Other Name: Control Arm

Detailed 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.

  Eligibility

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

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01783444

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 111 Study Locations
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: NCT01783444     History of Changes
Other Study ID Numbers: CRAD001Y2201
Study First Received: January 11, 2013
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration
Europe: European Medicines Agency
Lebanon: Ministry of Public Health
Saudi Arabia: Ministry of Health
Sweden: Medical Products Agency
Turkey: Ministry of Health

Keywords provided by Novartis:
Estrogen receptor positive, locally advanced, metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Capecitabine
Everolimus
Exemestane
Fluorouracil
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014