TUCATINIB for HER2-positive breast cancer | Breast cancer

Inclusion criteria

• {"criterion_text":"- Signed written informed consent"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Histologically confirmed primary invasive breast cancer"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- HER2 overexpression defined as circumferential membrane staining that is complete, intense and in >10% of invasive tumor cells (IHC 3+) on pre-treatment biopsy"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- WHO performance status 0-1"}
• {"criterion_text":"- Age (≥ 18 years of age)"}
• {"criterion_text":"- LVEF ≥50% measured by echocardiography or MUGA"}
• {"criterion_text":"- Eligible for neoadjuvant treatment"}

Exclusion criteria

• {"criterion_text":"- Inflammatory breast cancer, cT4 and/or cN3 tumors"}
• {"criterion_text":"- Contraindications for MRI"}
• {"criterion_text":"- Occult breast cancer (cT0)"}
• {"criterion_text":"- Bilateral breast cancer"}
• {"criterion_text":"- Current pregnancy or breastfeeding"}
• {"criterion_text":"- Current or previous other malignancy unless treated without systemic therapy and more than five years ago"}
• {"criterion_text":"- Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Known chronic liver disease"}
• {"criterion_text":"- History of inflammatory bowel disease or bowel resection"}

Primary endpoints

• {"endpoint_text":"- Incidence and severity of adverse events (all grades) until 30 days after last study treatment administration","definition_or_measurement_approach":"Measured as incidence and severity (all grades) of adverse events recorded until 30 days after last study treatment administration."}

Secondary endpoints

• {"endpoint_text":"- Incidence of serious adverse events until 30 days after last study treatment administration","definition_or_measurement_approach":"Measured as incidence of serious adverse events recorded until 30 days after last study treatment administration."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Progressive disease defined as 20% increase in ΔFTV or >20% increase in longest diameter on DCE-MRI or unequivocal new lesions on (18)F-FDG PET; incidence measured during neoadjuvant treatment."}
• {"endpoint_text":"- Incidence of dose reductions and treatment discontinuations","definition_or_measurement_approach":"Measured as incidence counts of dose reductions and treatment discontinuations during study treatment."}
• {"endpoint_text":"- Radiologic complete response defined as the absence of pathologic enhancement on contrast enhanced MRI breast","definition_or_measurement_approach":"Radiologic complete response assessed by contrast-enhanced breast MRI defined as absence of pathologic enhancement."}
• {"endpoint_text":"- Pathological complete response (ypT0/is N0) at surgery in patients treated without chemotherapy, and overall","definition_or_measurement_approach":"Pathological complete response defined as ypT0/is N0 at surgery; measured in patients treated without chemotherapy and overall."}
• {"endpoint_text":"- Residual Cancer burden (RCB, 0-III) at surgery in patients treated without chemotherapy, and overall","definition_or_measurement_approach":"Residual Cancer Burden assessed on surgical specimen using RCB scoring (0-III) in patients treated without chemotherapy and overall."}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"EFS defined as time from registration to disease progression resulting in inoperability, recurrence, or death from any cause; reported at 3, 5 and 10 years after registration."}
• {"endpoint_text":"- Overall survival (OS) defined as the time from registration to death from any cause at 3, 5 and 10 years after registration","definition_or_measurement_approach":"OS defined as time from registration to death from any cause; reported at 3, 5 and 10 years after registration."}

Netherlands

Earliest CTIS Part Ii Submission Date

23-09-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

50

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Seagen Inc. (wholly owned subsidiary of Pfizer Inc.)","duties_or_roles":"Source of monetary support","organisation_type":"Company"}