NCT02568839

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
202

participants targeted

Target at P75+ for phase_2

Timeline
34mo left

Started Nov 2014

Longer than P75 for phase_2

Geographic Reach
1 country

7 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress81%
Nov 2014Feb 2029

Study Start

First participant enrolled

November 1, 2014

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

September 21, 2015

Completed
15 days until next milestone

First Posted

Study publicly available on registry

October 6, 2015

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2019

Completed
10 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2029

Expected
Last Updated

August 13, 2020

Status Verified

August 1, 2020

Enrollment Period

4.3 years

First QC Date

September 21, 2015

Last Update Submit

August 11, 2020

Conditions

Early-Stage Breast CarcinomaHER-2 Positive Breast Cancer

Keywords

Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

  • Pathological objective response to primary medical treatment

    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

    At surgery

Secondary Outcomes (8)

  • Clinical/radiological objective response during neoadjuvant treatment

    During the 18-week treatment period before surgery

  • Event-free survival

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

  • Disease-free survival

    During the follow-up to 10 years

  • Breast cancer specific survival

    During the follow-up to 10 years

  • Overall survival

    During the follow-up to 10 years

  • +3 more secondary outcomes

Other Outcomes (1)

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

    5 years

Study Arms (2)

A standard treatment

ACTIVE COMPARATOR

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

B experimental treatment

EXPERIMENTAL

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

Interventions

docetaxel + trastuzumab sc + pertuzumabDRUG

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

Also known as: Herceptin SC, Perjeta
A standard treatment
trastuzumab emtansinDRUG

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

Also known as: Kadcyla
B experimental treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Dept. of Oncology, Örebro University Hospital

Örebro, Närke, Sweden

Location

Dept. of Oncology, Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Dept. of Oncology, Skåne University Hospital

Lund, Sweden

Location

Dept. of Oncology, Karolinska University Hospital

Stockholm, 17176, Sweden

Location

Dept. of Oncology, Sundsvall Hospital

Sundsvall, 851 86, Sweden

Location

Dept. of Oncology, University Hospital of Umeå

Umeå, Sweden

Location

Dept. of Oncology, Uppsala University Hospital

Uppsala, Sweden

Location

Related Publications (3)

  • Zhu Y, Zerdes I, Matikas A, Cruz IR, Bergqvist M, Elinder E, Bosch A, Lindman H, Einbeigi Z, Andersson A, Carlsson L, Dreifaldt AC, Isaksson-Friman E, Hellstrom M, Johansson H, Wang K, Bergh JCS, Hatschek T, Foukakis T. The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer: biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial. Breast Cancer Res Treat. 2024 Apr;204(2):299-308. doi: 10.1007/s10549-023-07200-x. Epub 2024 Jan 4.

    PMID: 38175448DERIVED

  • Matikas A, Johansson H, Gryback P, Bjohle J, Acs B, Boyaci C, Lekberg T, Fredholm H, Elinder E, Margolin S, Isaksson-Friman E, Bosch A, Lindman H, Adra J, Andersson A, Agartz S, Hellstrom M, Zerdes I, Hartman J, Bergh J, Hatschek T, Foukakis T. Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial. Clin Cancer Res. 2023 Feb 1;29(3):532-540. doi: 10.1158/1078-0432.CCR-22-2829.

    PMID: 36449695DERIVED

  • 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.

    PMID: 34165503DERIVED

Related Links

MeSH Terms

Conditions

Breast Neoplasms

Interventions

DocetaxelpertuzumabAdo-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesMaytansineMacrolidesLactonesLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsTrastuzumabAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Thomas Hatschek, Assoc prof

    Breast-sarcoma unit, Dept. of Oncology, Karolinska university hospital

    STUDY CHAIR

  • Jonas Bergh, Professor

    Dept. of Oncology-Pathology, Karolinska Institutet

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Sen. Consultant, MD, PhD, Assoc. professor

Study Record Dates

First Submitted

September 21, 2015

First Posted

October 6, 2015

Study Start

November 1, 2014

Primary Completion

February 1, 2019

Study Completion (Estimated)

February 1, 2029

Last Updated

August 13, 2020

Record last verified: 2020-08

Locations

SE(7)