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

NCT06162559 | Recruiting Phase 1

• 1 other identifier: N21TRV
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

neoadjuvant; HER2 positive; tucatinib; Breast cancer

Outcome Measures

Primary Outcomes (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

  an average of 8 months

Secondary Outcomes (8)

• Incidence of serious adverse events

  an average of 8 months

• Incidence of disease progression

  an average of 8 months

• Incidence of dose reductions and treatment discontinuations

  an average of 8 months

• Radiologic complete response

  an average of 8 months

• Pathological complete response

  an average of 8 months

Study Arms (1)

Tucatinib + trastuzumab + pertuzumab

EXPERIMENTAL

All 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.

Drug: Tucatinib; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

Tucatinib DRUG

Tucatinib 300mg is taken orally twice daily

Also known as: Tukysa

Tucatinib + trastuzumab + pertuzumab

Trastuzumab DRUG

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

Also known as: Herceptin

Tucatinib + trastuzumab + pertuzumab

Pertuzumab DRUG

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

Also known as: Perjeta

Tucatinib + trastuzumab + pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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.

You may not qualify if:

• 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
• Contraindications for MRI
• Inflammatory breast cancer, cT4 and/or cN3 tumors
• Occult breast cancer (cT0)

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Seagen Inc.: collaborator

Study Sites (1)

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinib; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 8, 2023
• Study Start: December 18, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): May 1, 2036
• Last Updated: January 11, 2024

Record last verified: 2024-01

Locations

NL (1)