Clinical trial NCT02568839: Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer
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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Early-Stage Breast Carcinoma
HER-2 Positive Breast Cancer
Keywords: Neoadjuvant therapy
Lead sponsor: Karolinska University Hospital
Sponsor class: OTHER
First posted: 2015-10-06
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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

Primary outcomes:
measure: Pathological objective response to primary medical treatment
timeFrame: At surgery
Secondary outcomes:
measure: Clinical/radiological objective response during neoadjuvant treatment
timeFrame: During the 18-week treatment period before surgery
measure: Event-free survival
timeFrame: All events from date of randomization until follow-up to 10 years
measure: Disease-free survival
timeFrame: During the follow-up to 10 years
measure: Breast cancer specific survival
timeFrame: During the follow-up to 10 years
measure: Overall survival
timeFrame: During the follow-up to 10 years
measure: Incidence of treatment-emergent adverse events [Safety and Tolerability]
timeFrame: During the 18-week period of treatment and until 30 days after termination and during the follow-up period up to 10 years
measure: Health Related Quality of life
timeFrame: From date of randomisation until follow-up to 5 years
measure: Frequency of breast-conserving surgery
timeFrame: At surgery
Other outcomes:
measure: Changes of morphological, functional and biological characteristics of early breast cancer before and after exposure to cytotoxic and targeted treatment
timeFrame: 5 years
Locations:
city: Örebro
country: Sweden
facility: Dept. of Oncology, Örebro University Hospital
state: Närke
city: Göteborg
country: Sweden
facility: Dept. of Oncology, Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Dept. of Oncology, Skåne University Hospital
city: Stockholm
country: Sweden
facility: Dept. of Oncology, Karolinska University Hospital
city: Sundsvall
country: Sweden
facility: Dept. of Oncology, Sundsvall Hospital
city: Umeå
country: Sweden
facility: Dept. of Oncology, University Hospital of Umeå
city: Uppsala
country: Sweden
facility: Dept. of Oncology, Uppsala University Hospital
Study officials:
affiliation: Breast-sarcoma unit, Dept. of Oncology, Karolinska university hospital
name: Thomas Hatschek, Assoc prof
role: STUDY_CHAIR
affiliation: Dept. of Oncology-Pathology, Karolinska Institutet
name: Jonas Bergh, Professor
role: STUDY_DIRECTOR
References:
citation: Hatschek T, Foukakis T, Bjohle J, Lekberg T, Fredholm H, Elinder E, Bosch A, Pekar G, Lindman H, Schiza A, Einbeigi Z, Adra J, Andersson A, Carlsson L, Dreifaldt AC, Isaksson-Friman E, Agartz S, Azavedo E, Gryback P, Hellstrom M, Johansson H, Maes C, Zerdes I, Hartman J, Brandberg Y, Bergh J. Neoadjuvant Trastuzumab, Pertuzumab, and Docetaxel vs Trastuzumab Emtansine in Patients With ERBB2-Positive Breast Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1360-1367. doi: 10.1001/jamaoncol.2021.1932.