Tucatinib in combination with Oral Etoposide (VP16) and Trastuzumab in Patients with metastatic HER2+ Breast cancer (TUC-TOC)

Phase 1

• Conditions: Metastatic HER2+ Breast cancer; MedDRA version: 20.1Level: PTClassification code: 10055113Term: Breast cancer metastatic Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2022-500743-20-00
• Lead Sponsor: Institut Curie

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-21
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

Disease progression under tucatinib-capecitabine-trastuzumab /OR / Medical contra-indication to initiate or continue capecitabine in association with tucatinib-trastuzumab (investigator’s decision based on patient medical history, DPD deficiency and/or capecitabine grade 2 toxicity or higher)., Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions, Left ventricular ejection fraction (LVEF) = 50% (within 4 weeks before inclusion), Adequate organ function (obtained within 14 days prior to treatment start) as evidenced by: oAbsolute neutrophil count (ANC) = 1.5 X 10^9/L oHemoglobin (Hgb) = 9 g/dL oPlatelet count = 100 X 10^9/L oBilirubin = 1.5 X upper limit of normal (ULN), except for patients with a documented history of Gilbert’s disease (= 2 X ULN) oAlanine aminotransferase (ALT), and aspartate aminotransferase (AST) = 2.5 X ULN (for patients with liver metastases = 5 X ULN); oAlkaline phosphatase (AP) = 3 X ULN (for patients with liver metastases, = 5 X ULN);oSerum creatinine = 1.5 mg/dL (133 µmol/L) or calculated creatinine clearance = 50 mL/min (using Cockcroft-Gault formula), If the patient is female: Women of childbearing potential (WCBP): negative serum pregnancy test. The patient must be willing to use effective methods of contraception. Patients must be postmenopausal, surgically infertile, or willing to use a physical barrier method of contraception in addition to an intrauterine device or hormonal contraception until at least 6 months after completion of study treatment, If the patient is male: Male patients must agree to use an acceptable method of contraception (e.g., condom) during the study and for 3 months after completion of investigational treatment,, Patients must be covered by a health insurance plan., Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol., Age > 18 years,, Histologically confirmed HER2+ breast carcinoma (ASCO/CAP guidelines) with archived tumor tissue available, Have a life expectancy of at least 3 months, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Participants must be able to swallow capsules, Participants must be able and willing to be available for the duration of the study and are willing to follow study procedures, Measurable disease, assessed by RECIST version 1, Patients with brain metastases are eligible: oUnless urgent treatment is required oIf time since WBRT is = 21 days prior to first dose of treatment, time since SRS is = 7 days prior to first dose of treatment, or time since surgical resection is = 28 days

Exclusion Criteria

Have previously been treated with: a.lapatinib within 12 months of starting study treatment (except in cases where lapatinib was given for = 21 days and was discontinued for reasons other than disease progression or severe toxicity) b.neratinib, afatinib, or other investigational HER2/ EGFR or HER2 TKI at any time previously (excepted for patients already under tucatinib who continue without interruption), Have evidence within 2 years of the start of study treatment of another malignancy that required systemic treatment. This does not apply to patients already under tucatinib who continue without interruption, Concomitant use of other agents for the treatment of cancer or any investigational agent(s), Women who are either pregnant, lactating, planning to get pregnant, Have a serious concomitant systemic disorder (eg, active infection or a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting, diarrhea, or profound immune suppression) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol, including but not limited to the following: (a) Have known human immunodeficiency virus (HIV) infection; (b) Active hepatitis B or C virus infection (screening required) or have other known chronic liver disease; (c) Severe renal impairment, interstitial lung disease (ILD), severe dyspnea at rest or requiring oxygen therapy, liver disease diagnosed with Child-Pugh A or higher cirrhosis or history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea, Have clinically significant cardiopulmonary disease such as: - ventricular arrhythmia requiring therapy, - uncontrolled hypertension (defined as persistent systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications), or - any history of symptomatic CHF osevere dyspnea at rest (CTCAE Grade 3 or above) due to complications of advanced malignancy, - hypoxia requiring supplementary oxygen therapy except when oxygen therapy is needed only for obstructive sleep apnea, - presence of = Grade 2 QTc prolongation on screening ECG, - conditions potentially resulting in drug-induced prolongation of the QT interval or torsade de pointes: 1. Congenital or acquired long QT syndrome, 2. Family history of sudden death, 3. History of previous drug induced QT prolongation, 4. Current use of medications with known and accepted associated risk of QT prolongation, Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment, Require therapy with warfarin or other coumarin derivatives (non-coumarin anticoagulants are allowed), Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medication, Patients with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent., Person deprived of liberty or placed under a legal protection regime with representation of the person., Patients who are pre-treated with tucatinib and who received a decreased dose of tucatinib (<300mg twice daily) are not eligible in the safety run-in phase, Inability to comply with medical monitoring of the trial for geographic, social or psychological reasons, Have used a strong CYP3A4 o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified