Status:

COMPLETED

Trastuzumab & Pertuzumab Followed by T-DM1 in MBC

Lead Sponsor:

Swiss Cancer Institute

Conditions:

Metastatic Breast Cancer

Eligibility:

FEMALE

18+ years

Phase:

PHASE2

Brief Summary

In HER2-positive metastatic breast cancer, trastuzumab based treatment is the standard of care as long as there are no contraindications to trastuzumab. Frequently, trastuzumab is being combined with ...

Detailed Description

OBJECTIVES: Primary -To evaluate the efficacy in terms of overall survival (OS) at 24 months of a chemotherapy-free dual HER2-inhibition with trastuzumab and pertuzumab (first-line) followed by T-DM...

Eligibility Criteria

Inclusion

  • SELECTION OF PATIENTS (MOST IMPORTANT CRITERIA)
  • Inclusion criteria for first-line therapy
  • • Histologically confirmed breast cancer with distant metastases
  • Note:
  • A biopsy from the primary tumor or a metastasis can be used for diagnosis.
  • Patients with non-measurable lesions are eligible.
  • Patients with inoperable, locally advanced breast cancer with lymph node metastases other than ipsilateral locoregional (axillary, infraclavicular, parasternal) or other distant metastases are eligible.
  • Patients with bone metastases with or without bone targeted therapy (bisphosphonates, denosumab) are eligible.
  • Patients with de-novo Stage IV disease are eligible.
  • HER2-positive tumor according to central pathology testing for HER2
  • Note:
  • A formalin-fixed paraffin-embedded (FFPE) biopsy from the primary tumor or a metastasis has to be used for HER2 status determination. If a biopsy is available from a metastasis, the HER2 testing should be performed using the metastasis.
  • Fine needle aspiration is not acceptable for HER 2 testing. • Women aged ≥18 years
  • • WHO performance status 0 to 2
  • Left Ventricular Ejection Fraction (LVEF) ≥50% as determined by either ECHO or MUGA
  • Adequate organ function, evidenced by the following laboratory results:
  • Neutrophils \>1.5x109/L, platelets \>100x109/L, hemoglobin ≥90g/L, total bilirubin ≤1.5xULN (unless the patients has documented Gilbert's disease), AST ≤3xULN, ALT ≤3xULN, AP ≤2.5xULN (except in patients with bone metastases: AP ≤5xULN), creatinine ≤1.5xULN
  • Exclusion criteria for first-line therapy
  • • Prior chemotherapy for inoperable locally advanced or metastatic breast cancer
  • Note:
  • Prior neoadjuvant/adjuvant chemotherapy is allowed if doses for anthracyclines have not exceeded 720mg/m2 and 240mg/m2 for epirubicin and doxorubicin, respectively.
  • \- Re-exposure to paclitaxel is permitted, if the last dose of taxane was given at least 1 year before randomization.
  • \- Re-exposure to vinorelbine is permitted, if the last dose of vinorelbine was given at least 1 year before randomization.
  • Prior anti-HER2 treatment for metastatic or inoperable breast cancer
  • Note:
  • Prior neoadjuvant/adjuvant anti-HER2 treatment with trastuzumab and/or lapatinib is allowed.
  • • More than one endocrine treatment line for metastatic or inoperable breast cancer exceeding a duration of 1 month
  • Note:
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  • Adjuvant endocrine treatment is not counted as one line.
  • Patients progressing on endocrine treatment: this specific endocrine treatment must have been stopped at least 2 weeks prior to randomization.
  • • Prior treatment with pertuzumab and/or T-DM1
  • • Known leptomeningeal or CNS metastases
  • Note:
  • A brain MRI or CT scan is mandatory in case of clinical suspicion of CNS metastases.
  • • Single bone metastasis treated with radiotherapy (if the bone metastasis is the only tumor lesion)
  • Inclusion criteria for second-line therapy • At least one dose of trial therapy in the first-line treatment phase of this trial
  • • • Proven disease progression on first-line therapy or radiotherapy of a bone metastasis
  • Notes:
  • First new parenchymal CNS metastases only do not count as progression requiring the initiation of second line trial treatment. Radiotherapy of a single area only for pain control is allowed and will not count as PD.
  • • Adequate organ function, evidenced by the following laboratory results: Neutrophils \>1.5x109/L, platelets \>100x109/L, hemoglobin ≥90g/L, total bilirubin ≤1.5xULN (unless the patients has documented Gilbert's disease), AST ≤3xULN, AP ≤2.5xULN (except in patients with bone metastases: AP ≤5xULN), creatinine ≤1.5ULN
  • • LVEF ≥50% as determined by either ECHO or MUGA
  • • QoL questionnaire has been completed.
  • Exclusion criteria for second-line therapy
  • • Termination of first-line therapy with trastuzumab/pertuzumab due to unacceptable toxicity without objective evidence of disease progression
  • • CNS metastases that are untreated, symptomatic, or require therapy to control symptoms, as well as a history of radiation, surgery, or other therapy, including steroids, to control symptoms from CNS metastases within 2 months (60 days) before registration
  • • Peripheral neuropathy of CTCAE grade ≥3
  • Interstitial lung disease (ILD) or pneumonitis grade ≥3
  • Any other adverse event which has not recovered to CTCAE grade ≤1 (except alopecia)

Exclusion

    Key Trial Info

    Start Date :

    March 3 2013

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    May 26 2020

    Estimated Enrollment :

    208 Patients enrolled

    Trial Details

    Trial ID

    NCT01835236

    Start Date

    March 3 2013

    End Date

    May 26 2020

    Last Update

    March 30 2021

    Active Locations (71)

    Enter a location and click search to find clinical trials sorted by distance.

    Page 1 of 18 (71 locations)

    1

    Hopital Sud - Amiens

    Amiens, France, 80054

    2

    ICO - Paul Papin

    Angers, France, 49933

    3

    Institut Sainte Catherine

    Avignon, France, 84918

    4

    Centre Hospitalier de Blois

    Blois, France, 41016

    Trastuzumab & Pertuzumab Followed by T-DM1 in MBC | DecenTrialz