Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer (BOLERO-3)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01007942
First received: November 2, 2009
Last updated: June 17, 2014
Last verified: June 2014

November 2, 2009
June 17, 2014
October 2009
June 2015   (final data collection date for primary outcome measure)
Progressive-free survival (PFS), defined as the time from the date of randomization to the date of first radiologically documented tumor progression or death from any cause, whichever occurs first. [ Time Frame: Every 6 months ] [ Designated as safety issue: No ]
Compare progressive-free survival (PFS) between the two treatment arms: everolimus, trastuzumab, and vinorelbine combination versus trastuzumab and vinorelbine combination [ Time Frame: 21.5 (251 PFS) to 32.5 (417 PFS) months after first randomization ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01007942 on ClinicalTrials.gov Archive Site
  • Overall survival (OS), defined as the time from date of randomization to the date of death from any cause. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Overall response rate (ORR) defined as the proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Patient reported outcome (PRO) questionnaires [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Clinical benefit rate (CBR) defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) lasting for at least 24 weeks. [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • Laboratory assessments (hematology, chemistry, coagulation), AEs graded by CTCAE version 3.0 or equivalent [ Time Frame: Continuous until 28 days after the last dose of study drug ] [ Designated as safety issue: Yes ]
  • Compare overall survival (OS) between the two treatment arms: everolimus, trastuzumab, and vinorelbine combination versus trastuzumab and vinorelbine combination. [ Time Frame: months after first randomization (384 OS events) ] [ Designated as safety issue: No ]
  • Compare objective response rate (ORR) between the two treatment arms. [ Time Frame: 55 months after first randomization (384 OS events) ] [ Designated as safety issue: No ]
  • Compare changes in Quality of Life (QoL) scores over time between the two treatment arms. [ Time Frame: at time of PFS analyses ] [ Designated as safety issue: No ]
  • Compare clinical benefit rate (CBR) between the two treatment arms. [ Time Frame: at time of Overall Survival (OS) analysis ] [ Designated as safety issue: No ]
  • Evaluate safety between the two treatment arms [ Time Frame: Monthly for certain pre-defined adverse event categories; at planned safety analysis after enrollment of first 60 patients (approximately 5 months after first randomization), and at PFS analyses ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Daily Everolimus in Combination With Trastuzumab and Vinorelbine in HER2/Neu Positive Women With Locally Advanced or Metastatic Breast Cancer
A Randomized Phase III, Double-blind, Placebo-controlled Multicenter Trial of Daily Everolimus in Combination With Trastuzumab and Vinorelbine, in Pretreated Women With HER2/Neu Over-expressing Locally Advanced or Metastatic Breast Cancer.

This phase III, double-blind, placebo-controlled multinational study will assess the combination everolimus, vinorelbine, and trastuzumab compared to the combination vinorelbine and trastuzumab with respect to progressive-free survival and over survival in HER2/neu positive women with locally advanced or metastatic breast cancer who are resistant to trastuzumab and have been pre-treated with a taxane.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • HER2/Neu Over-expressing Locally Advanced Breast Cancer
  • Metastatic Breast Cancer
  • Drug: everolimus, vinorelbine, trastuzumab
  • Drug: Placebo + vinorelbine + trastuzumab
  • Experimental: Everolimus + vinorelbine + trastuzumab
    Intervention: Drug: everolimus, vinorelbine, trastuzumab
  • Placebo Comparator: placebo + vinorelbine + trastuzumab
    Intervention: Drug: Placebo + vinorelbine + trastuzumab
André F, O'Regan R, Ozguroglu M, Toi M, Xu B, Jerusalem G, Masuda N, Wilks S, Arena F, Isaacs C, Yap YS, Papai Z, Lang I, Armstrong A, Lerzo G, White M, Shen K, Litton J, Chen D, Zhang Y, Ali S, Taran T, Gianni L. Everolimus for women with trastuzumab-resistant, HER2-positive, advanced breast cancer (BOLERO-3): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2014 May;15(6):580-91. doi: 10.1016/S1470-2045(14)70138-X. Epub 2014 Apr 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
570
June 2015
June 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
  • HER2+ status defined as IHC 3+ staining or in situ hybridization positive
  • Patients with resistance to trastuzumab
  • Prior taxane therapy
  • Patients with an ECOG performance status of 0 - 2
  • Patients with measurable disease as per RECIST criteria
  • Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-menopausal women must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study;
  • Patients must meet laboratory criteria defined in the study within 21 days prior to randomization

Exclusion Criteria:

  • Prior mTOR inhibitors or vinca alkaloid agents for the treatment of cancer
  • More than three prior chemotherapy lines for advanced disease.
  • Symptomatic CNS metastases or evidence of leptomeningeal disease. Previously treated asymptomatic CNS metastases are allowed provided that the last treatment for CNS metastases was completed >8 weeks prior to randomization
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
  • Peripheral neuropathy ≥ grade 2 at randomization
  • Active cardiac disease
  • History of cardiac dysfunction
  • Any 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
  • Known hypersensitivity to any study medication
  • Breastfeeding or pregnant

Other protocol-defined inclusion/exclusion criteria may ap

Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Japan,   Spain,   United Kingdom,   Turkey,   Thailand,   Argentina,   Australia,   Belgium,   China,   Czech Republic,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Mexico,   Poland,   Singapore,   Slovakia
 
NCT01007942
CRAD001W2301, 2008-008697-31
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP