A randomized phase II trial of pertuzumab in combination with trastuzumab with or without chemotherapy, both followed by T-DM1 in case of progression, in patients with HER2-positive metastatic breast cancer
- Conditions
- Breast cancer10006291
- Registration Number
- NL-OMON44863
- Lead Sponsor
- ICANCER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 26
- 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
- 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)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall Survival at 24 months</p><br>
- Secondary Outcome Measures
Name Time Method