Breast cancer
Conditions
Interventions
First line treatment
Arm A:
* Pertuzumab: 420 mg, every 3 weeks untill first progression. First dose 840 mg.
* Trastuzumab: 6 mg/kg, every 3 weeks untill first progression. First dose 8
mg/kg.
* Pati
q4w (at least 4 months unless
unacceptable toxicity or progressive disease is observed)
or
* Vinorelbine: 25 mg/m2 on day 1 and 8
thereafter 30 mg/m2 on day 1 and 8, q3w
(at least 4 months unless unacceptable toxicity or progressive disease is
observed)
Patients with hormone receptor positive disease should receive endocrine
Sponsors
UNICANCER
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Histologically confirmed breast cancer with distant metastases;Notes :;1. A biopsy from the primary tumor or a metastasis can be used for diagnosis.;2. Patients with non-measurable lesions are eligible.;3. Patients with inoperable, locally advanced breast cancer with lymph node metastases other than ipsilateral locoregional (axillary, infraclavicular, parasternal) or other distant metastases are eligible.;4. Patients with bone metastases with or without bone targeted therapy (bisphosphonates, denosumab) are eligible.;5. Patients with de-novo Stage IV disease are eligible.;- HER2-positive tumor according to central pathology testing for HER2;Note:;1. 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.;2. Fine needle aspiration is not acceptable for HER 2 testing.;- Women aged *18 years;- WHO performance status 0 to 2 (see Appendix 2);- Left Ventricular Ejection Fraction (LVEF) *50% as determined by either ECHO or MUGA;- Adequate organ function, evidenced by the following laboratory results:;Neutrophils >1.5x10^9/L, platelets >100x10^9/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;- 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 (please see Appendix 1.4, Determination and evaluation of new lesions).;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 >1.5x10^9/L, platelets >100x10^9/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 *1.5ULN;- LVEF *50% as determined by either ECHO or MUGA;- QoL questionnaire has been completed.;- Negative serum pregnancy test in women of childbearing potential
Exclusion criteria
Exclusion criteria: - Prior chemotherapy for inoperable locally advanced or metastatic breast cancer;Note:;Prior neoadjuvant/adjuvant chemotherapy is allowed if doses for anthracylines have not exceeded 720mg/m2 and 240mg/m2 for epirubicin and doxorubicin, respectivel.;- Reexposure to paclitaxel is permitted, if the last dose of taxane was given at least 1 year before randomisation.;- Reexposure to vinorelbine is permitted, if the last dose of vinorelbine was given at least 1 year before randomisation.;- 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:;1. Adjuvant endocrine treatment is not counted as one line.;2. 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);- 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 *4;- Any other adverse event which has not recovered to CTCAE grade *1 (except alopecia)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival at 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) OS at 24 months 2) Progression free survival (PFS) of first-line treatment ignoring first central nervous system lesion (CNS) lesion 3) PFS of second-line treatment 4) PFS of second-line treatment ignoring first CNS lesion 5) Time to failure of strategy (TFS) of first- plus second-line treatment 6) OS 7) Objective response (OR) of first-line treatment (based on investigator assessment) 8) Disease control (DC) of first-line treatment (based on investigator assessment) 9) OR of second-line treatment (based on investigator assessment) 10) DC of second-line treatment (based on investigator assessment) 11) Adverse events (AEs) according to the NCI CTCAE v4.0 of first-line treatment 12) AEs according to the NCI CTCAE v4.0 of second-line treatment 13) AEs grade *2 until first progression (ignoring first CNS lesion) 14) QoL 15) PFS of third-line treatment 16) Further treatment lines (third-line etc.) 17) Time to CNS metastases 18) Time from first CNS metastases to death | — |
Countries
Netherlands
Outcome results
None listed