Tucatinib plus trastuzumab and oxaliplatin-based chemotherapy or pembrolizumab-containing combinations for HER2+ gastrointestinal cancers
- Conditions
- Colorectal adenocarcinoma (CRC), Gastric adenocarcinoma, GEJ adenocarcinoma,
- Registration Number
- JPRN-jRCT2031220143
- Lead Sponsor
- Mayor JoAl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 40
1. Participants must have an unresectable or metastatic solid malignancy that is histologically or cytologically confirmed to be one of the tumor types listed below:
- Cohorts 1A, 1B, 1C, and 1D
- CRC
- Gastric adenocarcinoma
- GEJ adenocarcinoma
- Esophageal adenocarcinoma
- Cholangiocarcinoma
- Gallbladder carcinoma
- Cohorts 1E, 1F, 1G, and 2A
- Gastric adenocarcinoma
- GEJ adenocarcinoma
- Esophageal adenocarcinoma
- Cohort 2B
- CRC
Note: Cohorts 1A and 1B are not recruiting in Japan
2. Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G.
3. HER2+ disease, as determined by historic or local laboratory testing
4. Phase 1b cohorts: measurable or non-measurable disease according to RECIST v1.1 as determined by the investigator
Phase 2 cohorts: measurable disease according to RECIST v1.1 as determined by the investigator
5. Age 18 years or older at time of consent or >= the age of majority per regional requirements
6. Eastern Cooperative Oncology Group Performance Status score of 0 or 1.
1. History of known hypersensitivity to planned study treatment
2. Known to be positive for Hepatitis B or C
3. For Cohorts 2A and 2B: prior anti-HER2 therapies
For Cohorts 1E, 1F, 1G, 2A: Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137), and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1A and 1B (Not applicable in Japan):<br>- Incidence of renal dose-limiting toxicities (DLTs) <br>1C, 1E, 1F, and 1G: <br>- Type, incidence, severity, seriousness, and relatedness of adverse events (AEs), including DLTs, and laboratory abnormalities<br>- Vital signs and other relevant safety variables<br>1D:<br>- Type, incidence, severity, seriousness, and relatedness of AEs, including DLTs, and laboratory abnormalities<br>- Vital signs and other relevant safety variables<br>- Frequency of dose holds, dose reductions, and discontinuations of tucatinib, trastuzumab, and components of FOLFOX<br>Phase 2:<br>- Type, incidence, severity, seriousness, and relatedness of AEs, including DLTs, and laboratory abnormalities<br>- Vital signs and other relevant safety variables
- Secondary Outcome Measures
Name Time Method 1A and 1B (Not applicable in Japan):<br>- Type, incidence, severity, seriousness, and relatedness of adverse events (AEs) and laboratory abnormalities <br>- Vital signs and other relevant safety variables<br>- Change in glomerular filtration rate (GFR), as estimated using serum cystatin C, from baseline through 2 cycles of combination therapy<br>- PK parameters of tucatinib (including but not limited to AUClast, Cmax, Ctrough, and Tmax)<br>- PK parameters of oxaliplatin (including but not limited to AUClast, Cmax, Tmax)<br>1C, 1E, 1F, and 1G: <br>- ORR according to RECIST v1.1 per INV<br>- DOR (confirmed CR or PR) according to RECIST v1.1 per INV<br>- PFS according to RECIST v1.1 per INV<br>- OS<br>- PK parameters of tucatinib (including but not limited to Ctrough)<br>Phase 2:<br>- cORR (confirmed complete response [CR] or partial response [PR]) according to RECIST v1.1 per INV <br>- DOR (confirmed CR or PR) according to RECIST v1.1 per INV<br>- PFS according to RECIST v1.1 per INV<br>- OS