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Completed

NCT Number: NCT00876395

Everolimus in Combination With Trastuzumab and Paclitaxel in the Treatment of HER2 Positive Locally Advanced or Metastatic Breast Cancer

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

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasm Metastasis Neoplasms Neoplasms by Site Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, CABA, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.
  • Organ functions at time of inclusion.

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,

Treatment and study plan

Everolimus

Drug

Everolimus was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Other names: RAD001

Placebo

Drug

Everolimus placebo was administered in a continuous oral daily dosing of 10 mg (two 5-mg tablets).

Trastuzumab

Drug

Trastuzumab, 2 mg/kg weekly was used intravenously.

paclitaxel

Drug

Paclitaxel, 80 mg/m2 weekly was used intravenously.

Primary outcomes

  1. Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - Full Population

    Time frame: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months

    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 was assessed in the full patient population.

  2. Progression-free Survival (PFS) Per Investigators' Assessment Based on Local Radiology Review - (Hormone Receptor (HR)-Negative Population

    Time frame: date of randomization to the date of first documented tumor progression or death from any cause, whichever occurs first, reported between day of first patient randomized up to about 56 months

    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 was assessed in the HR-negative patient population.

Secondary outcomes

  1. Overall Survival (OS) - Full Population

    Time frame: up to about 76 months

    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 was performed either by telephone or clinic visit at least every 3 months. Additional survival updates were requested prior to interim or final analysis or prior to providing data to the health authorities. This was assessed in the full patient population.

  2. Overall Survival (OS) - HR-negative Population

    Time frame: up to about 76 months

    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 was performed either by telephone or clinic visit at least every 3 months. Additional survival updates were requested prior to interim or final analysis or prior to providing data to the health authorities. This was assessed in the HR-negative patient population.

  3. Overall Response Rate (ORR) - Full Population

    Time frame: up to about 23 months

    ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST. This was assessed in the full patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  4. Overall Response Rate (ORR) - HR-negative Population

    Time frame: up to about 23 months

    ORR is defined as the percentage of participants whose best overall response is either complete response (CR) or partial response (PR) according to RECIST. This was assessed in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  5. Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - Full Population

    Time frame: up to about 23 months

    CBR is defined as the percentage of participants 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 was assessed in the full patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  6. Clinical Benefit Rate (CBR) Equal to or Greater Than 24 Weeks - HR-negative Population

    Time frame: up to about 23 months

    CBR is defined as the percentage of participants 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 was assessed in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  7. Time to Overall Response Based on Investigator - Full Population

    Time frame: up to about 23 months

    Time to overall response defined as the time between date of randomization until first documented response Complete reseponse (CR) or partial response (PR) ), according to RECIST. This was assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  8. Time to Overall Response Based on Investigator - HR-negative Population

    Time frame: up to about 23 months

    Time to overall response defined as the time between date of randomization until first documented response Complete reseponse (CR) or partial response (PR) ), according to RECIST. This was assessed in the full patient population and in a subset of patients with Hormone Receptor Negative disease. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  9. Overall Response (OR) - Full Population

    Time frame: up to about 23 months

    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 documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  10. Overall Response (OR) - HR-negative Population

    Time frame: up to about 23 months

    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 documented response (CR or PR) and end date = date of event defined as the first documented progression or death due to underlying cause. This was assessed in the HR-negative patient population. Complete response is achieved when all lesions evaluated at Baseline are absent at subsequent visit.

  11. Everolimus Blood Level Concentrations at Steady States for Everolimus

    Time frame: predose, 2 hours post-dose at Cycle 2/Day 1, Cycle 2/Day 15, Cycle 2/ Day 22

    Blood levels at steady states for everolimus 10 mg/day and 5 mg/day. Only valid samples are included. Some patients had dose reduction to 5 mg daily dose therefore the everolimus blood concentration for them have been summarized separately. Cycle = 28 days

  12. Paclitaxel Plasma Concentrations

    Time frame: Cycle 2/Day 15 (Pre-infusion and end of infusion)

    Blood levels at steady states for everolimus/placebo

  13. Trastuzumab Serum Concentrations

    Time frame: Cycle 4/Day 1 (Pre-infusion and end of infusion)

    Blood levels at steady states for everolimus/placebo

  14. Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - Full Population

    Time frame: up to about 56 months

    Time to definitive deterioration of the ECOG PS by one category of the score from baseline will be performed. Baseline is the last available assessment on or before randomization date. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.

  15. Time to Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Score - HR-negative Population

    Time frame: up to about 56 months

    Time to definitive deterioration of the ECOG PS by one category of the score from baseline will be performed. Baseline is the last available assessment on or before randomization date. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at a subsequent time of measurement during the treatment period following the time point where the deterioration is observed.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: BOLERO-1

Important dates

Study start
2009
Primary completion
2014
Study completion
2017
First posted
Apr 6, 2009
Registry last updated
Dec 19, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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