Neoadjuvant trastuzumab, pertuzumab and tucatinib without chemotherapy in HER2-positive breast cancer: the TRAIN-4 study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Dec 2023 → ongoing

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Seagen Inc. (wholly owned subsidiary of Pfizer Inc.)

External identifiers

EU CT number

2024-518192-61-00

EudraCT number

2022-002784-29

ClinicalTrials.gov

NCT06162559

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Diagnosis, Therapy

To evaluate safety and feasibility of a neoadjuvant chemotherapy-free regimen with trastuzumab plus pertuzumab plus tucatinib in stage II-III HER2-positive breast cancer.

Secondary objectives 2

1. To estimate initial efficacy of a chemotherapy-free regimen with trastuzumab, pertuzumab and tucatinib in stage II-III HER2-positive breast cancer.
2. To evaluate the negative predictive value and feasibility of functional tumor volume decrease on DCE-MRI scan and SUVmax decrease on (18)F-FDG PET scan for pCR.

Conditions and MedDRA coding

Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Signed written informed consent
2. Histologically confirmed primary invasive breast cancer
3. Stage II – IIIA primary breast cancer according to TNM-staging (8th edition, AJCC); (largest tumor diameter DCE-MRI ≥ 2cm (cT2-3) and/or cN1-2 confirmed with FNA or histology)
4. HER2 overexpression defined as circumferential membrane staining that is complete, intense and in >10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy
5. Known estrogen- and progesterone-receptor expression of the invasive tumor a. 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
6. WHO performance status 0-1
7. Age (≥ 18 years of age)
8. LVEF ≥50% measured by echocardiography or MUGA
9. Eligible for neoadjuvant treatment
10. Laboratory requirements within 21 days prior to enrollment: a. Adequate bone marrow function (ANC ≥1.5 x 109/l, platelets ≥100 x 109/l); b. 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; c. 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

Exclusion criteria 10

1. Inflammatory breast cancer, cT4 and/or cN3 tumors
2. Occult breast cancer (cT0)
3. Bilateral breast cancer
4. Current pregnancy or breastfeeding
5. Current or previous other malignancy unless treated without systemic therapy and more than five years ago
6. Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
7. 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
8. Known chronic liver disease
9. History of inflammatory bowel disease or bowel resection
10. Contraindications for MRI

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and severity of adverse events (all grades) until 30 days after last study treatment administration

Secondary endpoints 8

1. Incidence of serious adverse events until 30 days after last study treatment administration
2. Incidence of progressive disease during neoadjuvant treatment -progressive disease: defined as 20% increase ΔFTV or >20% increase measured in the longest diameter on DCE-MRI or unequivocal new lesions on (18)F-FDG PET
3. Incidence of dose reductions and treatment discontinuations
4. Radiologic complete response defined as the absence of pathologic enhancement on contrast enhanced MRI breast
5. Pathological complete response (ypT0/is N0) at surgery in patients treated without chemotherapy, and overall
6. Residual Cancer burden (RCB, 0-III) at surgery in patients treated without chemotherapy, and overall
7. Event-free survival (EFS) defined as the interval from registration to disease progression resulting in inoperability, recurrence, or death from any cause, whichever comes first at 3, 5 and 10 years after registration
8. Overall survival (OS) defined as the time from registration to death from any cause at 3, 5 and 10 years after registration

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Sponsor organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Address

Plesmanlaan 121

City

Amsterdam

Postcode

1066 CX

Country

Netherlands

Scientific contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Gabe Sonke

Public contact point

Organisation

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Contact name

Gabe Sonke

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications