Tucatinib and trastuzumab in solid tumors with HER2 alterations.
- Conditions
- Previously Treated, Locally-Advanced Unresectable or Metastatic Solid Tumors Driven by HER2 Alterations.MedDRA version: 21.0Level: PTClassification code 10025697Term: Malignant neoplasm of ampulla of VaterSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10008593Term: CholangiocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10017614Term: Gallbladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10006187Term: Breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10008342Term: Cervix carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10046766Term: Uterine cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-004873-29-IT
- Lead Sponsor
- SEAGEN INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 270
1.Confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors.
2.Subjects with disease types other than breast cancer, biliary tract cancer, non-squamous NSCLC, and cervical cancer: Disease progression on or after the most recent systemic therapy for locally-advanced
unresectable or metastatic disease.
3.Subjects with any breast cancer subtype.
4.Subjects with biliary tract cancer: must have progressed on or after >or=1prior line of treatment (chemotherapy, endocrine therapy, or targeted therapy).
5.Subjects with non-squamous NSCLC: has relapsed from or is refractory to standard treatment or for which no standard treatment is available,
6.Subjects with cervical cancer.
7.Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for Standardization (ISO) accredited laboratory.
8.Have adequate hepatic function as defined by the following:
a. AST and ALT b.Total bilirubin 9.Have adequate baseline hematologic parameters as defined by:
a.Absolute neutrophil count (ANC) =1.0 × 109/L;
b.Platelet count =100 × 109/L; subjects with stable platelet count from 75 to 100 × 109/L may be included with approval from Medical Monitor;
c.Hemoglobin =9.0 g/dL; subjects with hemoglobin =8 and <9 g/dL may be included with approval from the Medical Monitor;
d.In subjects transfused before study entry, transfusion must be =14 days prior to start of therapy to establish adequate hematologic parameters independent from transfusion support.
10.Left ventricular ejection fraction (LVEF) >or=50% as assessed by echocardiogram or multiple-gated acquisition scan (MUGA) documented within Please refer to the protocol for full details.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 216
1. Subjects with breast cancer, GEC, or CRC whose disease shows HER2 amplification/overexpression.
2. Previous treatment with HER2-directed therapy; subjects with uterine serous carcinoma may have received prior trastuzumab.
3. Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in subjects with HR+ HER2-mutated breast cancer.
4. History of exposure to a >360 mg/m² doxorubicin-equivalent or >720 mg/m² epirubicin-equivalent cumulative dose of anthracyclines.
5. Treatment with any systemic anti-cancer therapy, radiation therapy, or experimental agent within 6. Have any toxicity related to prior cancer therapies that has not resolved to 8. Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment.
9. Known to be positive for hepatitis B by surface antigen expression. Known to be positive for hepatitis C infection. Subjects who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks.
10. Presence of known chronic liver disease.
11. Subjects known to be positive for human immunodeficiency virus (HIV) are excluded if they meet specific criteria (please refer to protocol for details).12. Are pregnant, breastfeeding, or planning a pregnancy from time of informed consent until 7 months after the final dose of any study drug, and, if applicable, for at least 2 years after the final dose of fulvestrant.
13. Have inability to swallow pills.
14. Have used a strong cytochrome P450 (CYP) 2C8 inhibitor within 5 half-lives of the inhibitor, or have used a strong CYP3A4 or CYP2C8 inducer within 5 days prior to start of treatment.
15. Have any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures.
16. History of another malignancy within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
17. Subjects with known CNS lesions must not have any of the following:
a. Any untreated brain lesions >2.0 cm in size, unless approved by the medical monitor,
b. Ongoing use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of >2 mg of dexamethasone (or equivalent). However, subjects on a chronic stable dose of c. Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related edema may pose risk to subject. Subjects who undergo local treatment for such lesions identified by screening brain magnetic resonance imaging (MRI) may still be eligible for the study,
d. Known or suspected leptomeningeal disease as documented by the investigator,
e. Have poorly controlled (>1/week) generalized or comp
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method