Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer (BOLERO-1)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00876395
First received: April 2, 2009
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

The purpose of this Phase III study is to confirm the value of adding everolimus to weekly paclitaxel and trastuzumab as treatment of HER2-overexpressing metastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Everolimus
Drug: Placebo
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 Phase III, Double-Blind, Placebo-Controlled Multicenter Trial of Everolimus in Combination With Trastuzumab and Paclitaxel, as First Line Therapy in Women With HER2 Positive Locally Advanced or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Every 8 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. This will be assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
    OS is defined as the time from date of randomization to the date of death due to any cause. For patients with documented progression, survival follow up will be performed either by telephone or clinic visit at least every 3 months. Additional survival updates may be requested, eg, prior to interim or final analysis or prior to providing data to the health authorities. This will be assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease.

  • Overall response rate (ORR) [ Time Frame: Every 8 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. This will be assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease.

  • Clinical benefit rate (CBR) [ Time Frame: Every 8 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. This will be assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease.

  • Time to overall response (Complete reseponse (CR) or partial response (PR) ) [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    Time to overall response defined as the time between date of randomization until first documented response (CR or PR), according to RECIST. This will be assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease.

  • Overall Response(OR) [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
    OR applies only to patients whose best OR was CR or PR. Start date = date of first documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. This will be assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease.

  • Blood levels at steady states for everolimus/placebo [ Time Frame: Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22, Cycle 4/Day 1 ] [ Designated as safety issue: No ]
    (Cmin and C2h) at Cycle 2/Day 1, Cycle 2/Day 15 & Cycle 2/Day 22, paclitaxel (Cmin and Cmax) at Cycle 2/Day 15 & trastuzumab (Cmin and Cmax) at Cycle 4/Day 1. Cycle = 28 days

  • Safety [ Time Frame: Continuous and every 8 weeks while on trial, 30 day safety update after last dose of study drug ] [ Designated as safety issue: Yes ]
    Incidence of adverse events, serious adverse events, shift from baseline in vital signs, laboratory results will be reported.


Enrollment: 719
Study Start Date: September 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus 10 mg daily
Everolimus 10 mg daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
Drug: Everolimus
Other Name: RAD001
Placebo Comparator: Placebo of everolimus daily
Placebo of everolimus daily in combination with paclitaxel 80mg/m2 weekly on days 1, 8, 15 and trastuzumab 2mg/kg weekly on days 1, 8, 15, 22
Drug: Placebo

  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 old).
  • Histologically or cytologically confirmed invasive breast carcinoma with local recurrence or radiological evidence of metastatic disease.
  • Must have at least one lesion that can be accurately measured or bone lesions in the absence of measurable disease.
  • HER2+ patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
  • Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is allowed but should be discontinued > 12 months prior to randomization.
  • Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
  • Documentation of negative pregnancy test.

Exclusion Criteria:

  • Prior mTOR inhibitors for the treatment of cancer.
  • Other anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy.
  • Patients with only non-measurable lesions other than bone metastasis (e.g. pleural effusion, ascites, etc).
  • Radiotherapy to ≥ 25% of the bone marrow within 4 weeks prior to randomization
  • History of central nervous system metastasis.
  • Impairment of gastrointestinal (GI) function or GI disease or active ulceration of the upper gastrointestinal tract.
  • Serious peripheral neuropathy.
  • Cardiac disease or dysfunction.
  • Uncontrolled hypertension.
  • HIV.
  • Pregnant, 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: NCT00876395

  Show 140 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00876395     History of Changes
Other Study ID Numbers: CRAD001J2301, 2008-006556-21
Study First Received: April 2, 2009
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Ministry of Health
Australia: Therapeutic Goods Administration
Belgium: Pharmaceutical Inspectorate
Brazil: National Health Surveillance Agency ANVISA
Canada: Health Canada
China: Food and Drug Administration
Columbia: Ministry of Health
Czech Republic: State Institute for Drug Control
Egypt: Ministry of Health, Drug Policy and Planning Center
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Greece: National Organization for Medicines
Hong Kong: Department of Health
Ireland: Medicines Board
Italy: local CA of the hospital of the Principle Investigator coordinator (legal Officer/director of the hospital of the PI)
Japan: Pharmaceuticals and Medical Devices Agency
Lebanon: Ministry of Health
Mexico: Ministry of Health
Peru: Ministry of Health
Russia:
South Africa: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)
Switzerland: Agency for Therapeutic Products
Taiwan: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Venezuela: Ministry of Health and Social Development
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Novartis:
Breast Cancer
HER2+
mTOR
everolimus
RAD001
first line
metastatic
locally advanced

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Trastuzumab
Sirolimus
Everolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on September 22, 2014