Cervical, Uterine, biliary tract, urothelial Cancers, NSCLC, Breast Cancer - Other solid tumors
Conditions
Interventions
- Tucatinib
300 mg orally twice daily
- Trastuzumab
Given into the vein (intravenously
IV). 8mg/kg IV on Cycle 1 Day 1, and 6mg/kg once every 21 days starting on Cycle 2 Day 1
- Fulvestrant
Given into the muscle (intramuscular
IM) once every 4 weeks starting from Cycle 1 Day 1, plus one dose on Cycle 1 Day 15. Only administered to participants with hormone-receptor positive breast cancer.
Sponsors
Ramos Jorge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors 2. Prior therapy: a. Participants with non-squamous NSCLC: Must have progressed during or after standard treatment or for which no standard treatment is available b. Participants with other disease types: Must have progressed during or after >=1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease 3. Disease progression during or after, or intolerance of, the most recent line of systemic therapy 4. 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, according to one of the following: a. HER2 overexpression/amplification from fresh or archival tumor tissue or blood b. Known activating HER2 mutations detected in fresh or archival tumor tissue or blood 5. Have measurable disease per RECIST v1.1 criteria according to investigator assessment 6. Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Exclusion criteria
Exclusion criteria: 1. Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression. 2. Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification 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 participants with HR+ HER2-mutated breast cancer 4. History of exposure to a 360 mg/m^2 doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines 5. Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within <=3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Confirmed objective response rate (cORR) per investigator assessment Note: cORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| - Disease control rate (DCR) per investigator assessment DCR is defined as the proportion of participants with confirmed CR, confirmed PR, or stable disease according to RECIST v1.1 - Duration of response (DOR) per investigator assessment DOR is defined as the time from first documentation of objective response of confirmed CR or confirmed PR to the first documentation of disease progression per RECIST v1.1 or death from any cause, whichever occurs first. - Progression-free survival (PFS) per investigator assessment PFS is defined as the time from the date of treatment initiation to the date of disease progression according to RECIST v1.1 or death from any cause, whichever occurs first. - Overall survival (OS) OS is defined as the time from treatment initiation to death due to any cause. - Incidence of adverse events (AEs) - Incidence of laboratory abnormalities - Incidence of dose alterations - Plasma concentrations of tucatinib | — |
Countries
Belgium, Italy, Japan, Poland, South Korea, Spain, the United Kingdom, United States
Contacts
Public ContactClinical contact
ICON Clinical Research GK
Outcome results
None listed