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Breast CancerPhase 1TRAIN-4NCT06162559

Neoadjuvant Trastuzumab, Pertuzumab and Tucatinib Without Chemotherapy in HER2-positive Breast Cancer: the TRAIN-4 Study

A Phase 1 study testing Tucatinib, Trastuzumab and Pertuzumab in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a single-center, phase 1b study evaluating the safety and feasibility of a neoadjuvant treatment with tucatinib, trastuzumab and pertuzumab in stage II-IIIA HER2-positive breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Tucatinib, Trastuzumab and Pertuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteNetherlands
Study dates
18 Dec 2023to May 2036
Phase
Phase 1
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

  • Signed written informed consent
  • Histologically confirmed primary invasive breast cancer
  • Stage II - IIIA primary breast cancer according to TNM-staging (8th edition, AJCC); (largest tumor diameter on DCE-MRI ≥ 2cm (cT2-3) and/or cN1-2 confirmed with FNA or histology)
  • HER2 overexpression defined as circumferential membrane staining that is complete, intense and in >10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy
  • Known estrogen- and progesterone-receptor expression of the invasive tumor
  • ER-negative or PR-negative is defined as <10% of invasive tumor cell nuclei are immunoreactive in the presence of evidence that the sample can express ER and/or PR
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  • WHO performance status 0-1
  • Age ≥ 18 years
  • LVEF ≥50% measured by echocardiography or MUGA
  • Eligible for neoadjuvant treatment
  • Laboratory requirements within 21 days prior to enrollment:
  • Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l);
  • Adequate hepatic function (ALAT, ASAT and bilirubin ≤2.5 times upper limit of normal). Subjects with Gilbert's syndrome may have a total bilirubin ≥2.5 × the ULN range, if no evidence of biliary obstruction exists.
  • Adequate renal function: creatinine clearance >50 ml/min estimated using the Cockcroft-Gault equation or MDRD equation, or based on a 24-hour urine collection measurement.

Who cannot join

  • Current pregnancy or breastfeeding
  • Current or previous other malignancy unless treated without systemic therapy and more than five years ago
  • Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  • Use of a strong CYP3A4 or CYP2C8 inhibitor within five half-lives of the inhibitor, or used a strong CYP3A4 or CYP2C8 inducer within five days prior to first dose of study treatment
  • Known chronic liver disease
  • History of inflammatory bowel disease or bowel resection
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  • Contraindications for MRI
  • Inflammatory breast cancer, cT4 and/or cN3 tumors
  • Occult breast cancer (cT0)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Netherlands1 site, 1 recruiting

  • Netherlands Cancer Institute

    Amsterdam, 1066CX

    Gabe Sonke, MD PhD, +31205129111, trainstudies@nki.nl

    Recruiting

Other trials in Netherlands

About this study

This is a single-center, phase 1b study evaluating the safety and feasibility of a neoadjuvant treatment with tucatinib, trastuzumab and pertuzumab in stage II-IIIA HER2-positive breast cancer.

Read the detailed description

High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. However, a subset of patients with stage II-III HER2-positive breast cancer can be treated with HER2-blockade alone. These patients can potentially be totally spared from chemotherapy-associated toxicity. The proportion of patients whom can successfully be treated without chemotherapy could potentially be increased by selecting great responders using DCE-MRI and by adding tucatinib to trastuzumab and pertuzumab alone. The aim of this study is to evaluate the safety and efficacy of neoadjuvant treatment with tucatinib, trastuzumab and pertuzumab.

Conditions
Breast Cancer
Being tested
Tucatinib, Trastuzumab, Pertuzumab
Keywords
neoadjuvant, HER2 positive, tucatinib, Breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

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

  • TucatinibDrug

    Also called Tukysa

    Tucatinib 300mg is taken orally twice daily

  • TrastuzumabDrug

    Also called Herceptin

    Trastuzumab 6mg/kg is administered intravenously on day 1 (loading dose 8mg/kg) or subcutaneously 600mg on day 1 of each cycle

  • PertuzumabDrug

    Also called Perjeta

    Pertuzumab 420mg is administered intravenously on day 1 (loading dose 840mg) or subcutaneously 600mg/kg (loading dose 1200mg) on day 1 of each cycle

Study groups in NCT06162559
Study groupRoleWhat they receive
Tucatinib + trastuzumab + pertuzumabExperimentalAll patients receive neoadjuvant treatment consisting of trastuzumab, pertuzumab and tucatinib. Patients with hormone receptor positive disease receive concurrent endocrine therapy with an aromatase-inhibitor. Premenopausal women are concurrently treated with a LHRH-agonist. In case of functional tumor volume decrease of at least 65% (responders) after the first three cycles, patients continue treatment for six more cycles of the chemotherapy-free regimen. If tumor response is <65% (non-responders), patients will switch to receive six cycles paclitaxel, carboplatin, trastuzumab and pertuzumab. This is considered non-investigational treatment.
Receives: Drug: Tucatinib; Drug: Trastuzumab; Drug: Pertuzumab

What is being measured

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

  1. Incidence and severity of adverse events

    Number of patients with adverse events and severity of adverse events (all grades; CTCAE v5.0) until 30 days after last study treatment administration

    Measured: an average of 8 months

Secondary outcomes (8)

  1. Incidence of serious adverse events

    Number of patients with serious adverse events until 30 days after last study treatment administration

    Measured: an average of 8 months

  2. Incidence of disease progression

    Number of patients with progressive disease during neoadjuvant treatment. Progressive disease is defined as 20% increase in ∆FTV or >20% increase measured in the longest diameter on DCE-MRI or unequivocal new lesions on (18)F-FDG PET

    Measured: an average of 8 months

  3. Incidence of dose reductions and treatment discontinuations

    Number of patients with dose reductions and treatment discontinuations

    Measured: an average of 8 months

  4. Radiologic complete response

    Number of patients with a radiologic complete response defined as the absence of pathologic enhancement on contrast enhanced MRI breast

    Measured: an average of 8 months

  5. Pathological complete response

    Number of patients with a pathological complete response (ypT0/is N0) at surgery in patients treated without chemotherapy, and overall

    Measured: an average of 8 months

  6. Residual Cancer Burden

    Residual Cancer burden (RCB, 0-III) at surgery in patients treated without chemotherapy, and overall

    Measured: an average of 8 months

  7. Event-free survival

    Number of patients without progression or disease recurrence, second primary or death at 3, 5 and 10 years after registration

    Measured: 3, 5, 10 years

  8. Overall survival

    Number of patients alive at 3, 5 and 10 years after registration

    Measured: 3, 5, 10 years

Timeline

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

  1. First posted8 Dec 2023
  2. Study start18 Dec 2023
  3. Primary completionAug 2026 (estimated)
  4. Study completionMay 2036 (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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06162559
Sponsor's protocol ID
N21TRV
Acronym
TRAIN-4
Status last verified
Jan 2024
First submitted
29 Nov 2023
Last updated
11 Jan 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tucatinib, Trastuzumab and Pertuzumab in people with Breast Cancer, run by The Netherlands Cancer Institute at 1 site in Netherlands.

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 14 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 11 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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 phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of adverse events (time frame: an average of 8 months). 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 NCT06162559.

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 11 Jan 2024.

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