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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
Sponsor:
Information provided by (Responsible Party):
Thomas Hatschek, Karolinska University Hospital

Brief Summary:

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

Detailed Description:

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:

  1. PET-CT using FDG, confined to the chest, is performed before start, and after the 2nd and 6th course (functional imaging, optional).
  2. 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
  3. Blood samples are collected repeatedly during the ongoing treatment and yearly follow-up
  4. FNAs from metastases in case of recurrence during follow-up

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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
Other Names:
  • Herceptin SC
  • Perjeta

Experimental: B

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Frequency of breast-conserving surgery [ Time Frame: At surgery ]
    Type of surgery is recorded at the point of surgery


Other Outcome Measures:
  1. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent
  2. Patients with breast cancer confirmed by histology, characterized by immunohistochemistry for ER, PR, HER2 and proliferation marker
  3. Tumor and blood samples available. HER2 type confirmed by ISH
  4. Age 18 years or older. Elderly patients in condition adequate for planned therapy
  5. Primary breast cancer >20mm in diameter and/or verified lymph node metastases
  6. Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
  7. LVEF ≥55%
  8. ECOG performance status 0-1
  9. Primary breast cancer as defined in p. 5 plus at most 2 morphologically characterized well-defined distant metastases accessible for stereotactic radiotherapy, provided that this treatment is available

Exclusion Criteria:

  1. Distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum
  2. Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix
  3. Patients in child-bearing age without adequate contraception
  4. Pregnancy or lactation
  5. Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders

Information from the National Library of Medicine

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


Contacts
Contact: Mats Hellström, Coordinator +46 8 517 ext 73677 mats.hellstrom@karolinska.se
Contact: Yvonne Larsén, Monitor +46 8 517 ext 70901 yvonne.larsen@karolinska.se

Locations
Sweden
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       kajsa.holgersson@vgregion.se   
Principal Investigator: Zakaria Einbeigi, MD, PhD         
Dept. of Oncology, Skåne University Hospital Recruiting
Lund, Sweden
Contact: Suzy Lindberg, RN       suzylindberg@skane.se   
Principal Investigator: Eva Karlsson, MD, PhD         
Dept. of Oncology, Karolinska University Hospital Recruiting
Stockholm, Sweden, 17176
Contact: Ingrid Lundin, RN       ingrid.lundin@karolinska.se   
Contact: Gittan Nässén, RN       birgitta.nassen@karolinska.se   
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       christine.naslund@lvn.se   
Principal Investigator: Lena Carlsson, MD         
Dept. of Oncology, University Hospital of Umeå Not yet recruiting
Umeå, Sweden
Contact: Lena Bylund, RN       lena.bylund@vll.se   
Principal Investigator: Anne Andersson, MD         
Dept. of Oncology, Uppsala University Hospital Not yet recruiting
Uppsala, Sweden
Contact: Camilla Taavo, RN       camilla.taavo@akademiska.se   
Principal Investigator: Henrik Lindman, Assoc prof         
Sponsors and Collaborators
Thomas Hatschek
Investigators
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

Responsible Party: Thomas Hatschek, Sen. Consultant, MD, PhD, Assoc. professor, Karolinska University Hospital
ClinicalTrials.gov Identifier: NCT02568839     History of Changes
Other Study ID Numbers: PREDIX HER2
First Posted: October 6, 2015    Key Record Dates
Last Update Posted: September 8, 2016
Last Verified: September 2016

Keywords provided by Thomas Hatschek, Karolinska University Hospital:
Neoadjuvant therapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Pertuzumab
Ado-trastuzumab emtansine
Trastuzumab
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action