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Early-Stage Breast CarcinomaPhase 2/3PREDIX HER2NCT02568839

Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer

A Phase 2/3 study testing docetaxel + trastuzumab sc + pertuzumab and trastuzumab emtansin in people with Early-Stage Breast Carcinoma and HER-2 Positive Breast Cancer, run by Thomas Hatschek at 7 sites in Sweden.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
docetaxel + trastuzumab sc + pertuzumab and trastuzumab emtansin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
202 participants
Where
7 sitesSweden
Study dates
Nov 2014to Feb 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Sweden7 sites

  • Dept. of Oncology, Sahlgrenska University Hospital

    Gothenburg, 413 45

  • Dept. of Oncology, Skåne University Hospital

    Lund

  • Dept. of Oncology, Örebro University Hospital

    Örebro, Närke

  • Dept. of Oncology, Karolinska University Hospital

    Stockholm, 17176

  • Dept. of Oncology, Sundsvall Hospital

    Sundsvall, 851 86

  • Dept. of Oncology, University Hospital of Umeå

    Umeå

  • Dept. of Oncology, Uppsala University Hospital

    Uppsala

Other trials in Sweden

About this study

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

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.

Read the 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
Being tested
docetaxel + trastuzumab sc + pertuzumab, trastuzumab emtansin
Keywords
Neoadjuvant therapy
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • docetaxel + trastuzumab sc + pertuzumabDrug

    Also called Herceptin SC, Perjeta

    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 emtansinDrug

    Also called Kadcyla

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

Study groups in NCT02568839
Study groupRoleWhat they receive
A standard treatmentActive comparatordocetaxel + 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.
Receives: Drug: docetaxel + trastuzumab sc + pertuzumab
B experimental treatmentExperimentaltrastuzumab 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.
Receives: Drug: trastuzumab emtansin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: At surgery

Secondary outcomes (8)

  1. Clinical/radiological objective response during neoadjuvant treatment

    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

    Measured: During the 18-week treatment period before surgery

  2. Event-free survival

    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

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

  3. Disease-free survival

    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

    Measured: During the follow-up to 10 years

  4. Breast cancer specific survival

    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

    Measured: During the follow-up to 10 years

  5. Overall survival

    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

    Measured: During the follow-up to 10 years

  6. Incidence of treatment-emergent adverse events [Safety and Tolerability]

    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

    Measured: During the 18-week period of treatment and until 30 days after termination and during the follow-up period up to 10 years

  7. Health Related Quality of life

    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

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

  8. Frequency of breast-conserving surgery

    Type of surgery is recorded at the time of surgery

    Measured: At surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2015 (estimated)
  2. Study startNov 2014
  3. Primary completionFeb 2019
  4. Study completionFeb 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02568839
Sponsor's protocol ID
PREDIX HER2
Acronym
PREDIX HER2
Status last verified
Aug 2020
First submitted
21 Sep 2015
Last updated
13 Aug 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 38175448

  • 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.

    PubMed 36449695

  • 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.

    PubMed 34165503

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing docetaxel + trastuzumab sc + pertuzumab and trastuzumab emtansin in people with Early-Stage Breast Carcinoma and HER-2 Positive Breast Cancer, run by Thomas Hatschek at 7 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 13 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathological objective response to primary medical treatment (time frame: At surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02568839, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2020.

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