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Active, Not Recruiting

NCT Number: NCT02568839

Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Early-Stage Breast Carcinoma Breast Diseases Breast Neoplasms HER-2 Positive Breast Cancer Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Dept. of Oncology, Örebro University Hospital, Örebro, Närke, Sweden

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Written informed consent
  • Patients with breast cancer confirmed by histology, characterized by immunohistochemistry for ER, PR, HER2 and proliferation marker
  • Tumor and blood samples available. HER2 type confirmed by ISH
  • Age 18 years or older. Elderly patients in condition adequate for planned therapy
  • Primary breast cancer >20mm in diameter and/or verified lymph node metastases
  • Adequate bone marrow, renal, hepatic and cardiac functions and no other uncontrolled medical or psychiatric disorders
  • LVEF ≥55%
  • ECOG performance status 0-1
  • 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

  • Distant metastases, including node metastases in the contralateral thoracic region or in the mediastinum
  • 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
  • Patients in child-bearing age without adequate contraception
  • Pregnancy or lactation
  • Uncontrolled hypertension, heart, liver, kidney related or other medical or psychiatric disorders

Treatment and study plan

docetaxel + trastuzumab sc + pertuzumab

Drug

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

trastuzumab emtansin

Drug

trastuzumab emtansine 3.6 mg/kg IV, repeated every 3 weeks, 6 courses

Other names: Kadcyla

Primary outcomes

  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 outcomes

  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. Event-free survival

    Time frame: All events from date of randomization until follow-up to 10 years

    Time frame for reporting is from date of randomization until first reported event, including disease progression, documented first recurrence, first contralateral breast cancer, first cancer of other origin, or death of any cause, whatever occurs first

  3. Disease-free survival

    Time frame: During the follow-up to 10 years

    Time frame for reporting is between date of surgery and 10 years follow-up. Date of detection of metastasis will be reported within 12 months after occurence

  4. Breast cancer specific survival

    Time frame: During the follow-up to 10 years

    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

  5. Overall survival

    Time frame: During the follow-up to 10 years

    Time frame for reporting is between date of surgery and 10 years follow-up. Date of death will be reported within 12 months after occurence

  6. 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 10 years

    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 10 years of follow-up after surgery

  7. Health Related Quality of life

    Time frame: From date of randomisation until follow-up to 5 years

    Repeated assessments using EOTC QLQ-C30 and BR23 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 10 years. Time frame covers the 18-week period of preoperative treatment and 10 years follow-up period after surgery

  8. Frequency of breast-conserving surgery

    Time frame: At surgery

    Type of surgery is recorded at the time of surgery

Other outcomes

  1. Changes of morphological, functional and biological characteristics of early breast cancer before and after exposure to cytotoxic and targeted treatment

    Time frame: 5 years

    Includes genomics, proteomics and other biomarker-related analyses on core biopsies 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. Functional imaging using 18F-FDG PET-CT is performed at baseline and after the 2nd and 6th treatment course.

Sponsors and collaborators

Lead sponsor

Thomas Hatschek

Other

Registry information

Official study 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

Acronym: PREDIX HER2

Important dates

Study start
2014
Primary completion
2019
Study completion
2029
First posted
Oct 6, 2015
Registry last updated
Aug 13, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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