Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer (PREDIX HER2)
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|ClinicalTrials.gov Identifier: NCT02568839|
Recruitment Status : Recruiting
First Posted : October 6, 2015
Last Update Posted : September 8, 2016
The purpose of this trial is to evaluate efficacy and toxicity of either the combination of docetaxel, trastuzumab sc and pertuzumab (arm A) or trastuzumab emtansin (arm B). Switch of therapy to the opposite treatment alternative is applicable in case of lack of response after two courses of treatment, or for medical reasons under exceptional circumstances (drug reaction, other medical conditions) at any point. After termination of the primary treatment follow-up for five years.
A translational subprotocol is a mandatory part of the study protocol, with exception for the use of PET-CT evaluations.
|Condition or disease||Intervention/treatment||Phase|
|Early-Stage Breast Carcinoma HER-2 Positive Breast Cancer||Drug: docetaxel + trastuzumab sc + pertuzumab Drug: trastuzumab emtansin||Phase 2 Phase 3|
Patients with HER2-positive tumors >20 mm or verfied regional lymph node metastases are randomized to either arm A, the combination of docetaxel, trastuzumab sc (Herceptin SC®) and pertuzumab (Perjeta®) or arm B, trastuzumab emtansin (Kadcyla®). Switch to the opposite treatment is performed in case of lack of response after evaluations with mammography and ultrasound, alternatively MRI breast after the 2nd, 4th and 6th course of treatment.
Postoperative treatment, trastuzumab, radiotherapy, eventual endocrine treatment) according to standard guidelines. Structured follow-up visits yearly for five years, including reporting of persistent treatment-related toxicity, HRQoL, recurrence and death.
The trial contains also a translational subprotocol:
- PET-CT using FDG, confined to the chest, is performed before start, and after the 2nd and 6th course (functional imaging, optional).
- Core biopsies from the tumor are collected before start and after the 2nd course of treatment. If residual tissue is available, samples are collected from the surgical sample
- Blood samples are collected repeatedly during the ongoing treatment and yearly follow-up
- FNAs from metastases in case of recurrence during follow-up
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||PREDIX HER2 - Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer. Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes|
|Study Start Date :||November 2014|
|Estimated Primary Completion Date :||December 2017|
|Estimated Study Completion Date :||December 2022|
Active Comparator: A
docetaxel + trastuzumab sc + pertuzumab. Treatment with all three drugs is given on day 1, repeated every three weeks. Six courses of preoperative treatment. Response evaluations after every 2nd course. In case of no change (NC), treatment is switched to arm B.
Postoperatively, patients receive 2 courses of treatment with the combination epirubicin + cyclophosphamide (EC), followed by adjuvant trastuzumab, radiotherapy, eventually endocrine treatment.
Drug: docetaxel + trastuzumab sc + pertuzumab
docetaxel 75-100 mg IV + trastuzumab sc 5 ml (600 mg) SC + pertuzumab 840 mg IV starting dose, subsequently 420 mg IV, repeated every 3 weeks, 6 courses
trastuzumab emtansine. Treatment is given on day 1, repeated every three weeks. Six courses of preoperative treatment. Response evaluations after every 2nd course. In case of no change (NC), treatment is switched to arm A.
Postoperatively, patients receive 4 courses of treatment with the combination epirubicin + cyclophosphamide (EC), followed by adjuvant trastuzumab, radiotherapy, eventually endocrine treatment.
Drug: trastuzumab emtansin
trastuzumab emtansine 3.6 mg/kg IV, repeated every 3 weeks, 6 courses
Other Name: Kadcyla
- Pathological objective response to primary medical treatment [ Time Frame: At surgery ]Efficacy measure after 18 weeks of preoperative treatment, starting from the start of preoperative medical treatment until the date of surgery. Outcome should be received within not more than 4 weeks post surgery
- Clinical/radiological objective response during neoadjuvant treatment [ Time Frame: During the 18-week treatment period before surgery ]Clinical measurements with caliper, radiological evaluations with mammography and ultrasound, alternately MRI, within 6 weeks before start, and 14 days after 3-weekly courses 2, 4 and 6; PET-CT within 2 weeks before start, and 16 days after courses 2 and 6. Time frame for these response evaluations is between between week 4 and week 18 of preoperative treatment
- Disease-free survival [ Time Frame: During the follow-up period up to 60 months ]Time frame for reporting is between date of surgery and 60 months follow-up. Date of detection of metastasis will be reported within 12 months after occurence
- Breast cancer specific survival [ Time Frame: During the follow-up period up to 60 months ]Time frame for reporting is between date of surgery and 60 months follow-up. Date and cause of death will be reported within 12 months after occurence
- Overall survival [ Time Frame: During the follow-up period up to 60 months ]Time frame for reporting is between date of surgery and 60 months follow-up. Date of death will be reported within 12 months after occurence
- Incidence of treatment-emergent adverse events [Safety and Tolerability] [ Time Frame: During the 18-week period of treatment and until 30 days after termination and during the follow-up period up to 60 months ]Time frame for reporting of acute side effects is from start of treatment until 30 days after termination of the treatment, totally 22 weeks. Late side effects are reported within 60 months post surgery. Cardiac toxicity is given special attention during the entire period. Echocardiograms and ECGs are performed within 6 weeks before start of treatment, after 16 weeks of treatment before surgery, and then every 3 months during postoperative treatment with trastuzumab the 1st postoperative year; thereafter every 12 months until 60 months of follow-up after surgery
- Quality of life [ Time Frame: During the 18-week treatment period and during the follow-up period up to 60 months ]Repeated HRQoL assessments during the treatment period, before randomization and after courses 2, 4 and 6, 3 months post surgery and annually during the follow-up period up to 60 months. Time frame covers the 18-week period of preoperative treatment and 60 months follow-up period after surgery
- Frequency of breast-conserving surgery [ Time Frame: At surgery ]Type of surgery is recorded at the point of surgery
- Morphological, functional and biological characteristics of tumors exposed to cytotoxic and targeted treatment of early breast cancer [ Time Frame: During treatment and annually during the post-surgical follow-up period up to 60 months ]Includes core biopsy and blood samples before start and after two courses of treatment, collection of tumor samples from the surgical specimen at the date of operation, blood samples in connection with annual follow-up visits and FNA and blood samples in case of recurrence. Time frame for collection of biological samples from start of preoperative treatment until 60 months of follow-up post surgery. Planned analyses cover genomics, proteomics, studies of tumor stroma, angiogenesis and tumor stem cells
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02568839
|Contact: Mats Hellström, Coordinator||+46 8 517 ext email@example.com|
|Contact: Yvonne Larsén, Monitor||+46 8 517 ext firstname.lastname@example.org|
|Dept. of Oncology, Örebro University Hospital||Not yet recruiting|
|Örebro, Närke, Sweden|
|Principal Investigator: Johan Ahlgren, Assoc prof|
|Dept. of Oncology, Sahlgrenska University Hospital||Recruiting|
|Göteborg, Sweden, 413 45|
|Contact: Kajsa Holgersson, RN email@example.com|
|Principal Investigator: Zakaria Einbeigi, MD, PhD|
|Dept. of Oncology, Skåne University Hospital||Recruiting|
|Contact: Suzy Lindberg, RN firstname.lastname@example.org|
|Principal Investigator: Eva Karlsson, MD, PhD|
|Dept. of Oncology, Karolinska University Hospital||Recruiting|
|Stockholm, Sweden, 17176|
|Contact: Ingrid Lundin, RN email@example.com|
|Contact: Gittan Nässén, RN firstname.lastname@example.org|
|Principal Investigator: Theodoros Foukakis, Assoc prof|
|Sub-Investigator: Ellinor Elinder, MD|
|Dept. of Oncology, Sundsvall Hospital||Recruiting|
|Sundsvall, Sweden, 851 86|
|Contact: Christin Näslund, RN email@example.com|
|Principal Investigator: Lena Carlsson, MD|
|Dept. of Oncology, University Hospital of Umeå||Not yet recruiting|
|Contact: Lena Bylund, RN firstname.lastname@example.org|
|Principal Investigator: Anne Andersson, MD|
|Dept. of Oncology, Uppsala University Hospital||Not yet recruiting|
|Contact: Camilla Taavo, RN email@example.com|
|Principal Investigator: Henrik Lindman, Assoc prof|
|Study Chair:||Thomas Hatschek, Assoc prof||Breast-sarcoma unit, Dept. of Oncology, Karolinska university hospital|
|Study Director:||Jonas Bergh, Professor||Dept. of Oncology-Pathology, Karolinska Institutet|