Tucatinib plus trastuzumab and oxaliplatin-based chemotherapy or pembrolizumab-containing combinations for HER2+ gastrointestinal cancers

JRCT ID: jRCT2031220143

Registered date:18/06/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Colorectal adenocarcinoma (CRC), Gastric adenocarcinoma, GEJ adenocarcinoma,
• Date of first enrollment: 08/07/2022
• Target sample size: 40
• Countries of recruitment: US,Japan
• Study type: Interventional

Intervention(s)

Tucatinib
- For Cohort 1A, 150 mg will be administered twice daily by mouth (orally) from Cycle 1 Day 8 onwards. For all other cohorts, 300 mg (or intermediate dose) will be given orally twice daily starting on Cycle 1 Day 1.
Trastuzumab
- Cohorts 1A and 1B: a 6 mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 Day 1, followed by a dose of 4 mg/kg IV every 2 weeks starting on Cycle 2 Day 1. Cohorts 1C, 1D, 1E, 1F, 1G,2A , and 2B: an 8 mg/kg loading dose will be administered IV on Cycle 1 Day 1, followed by a dose of 6 mg/kg IV every 3 weeks thereafter.
Oxaliplatin
- 85 mg/m^2 given IV every 2 weeks for cohorts using FOLFOX. For cohorts using CAPOX regimen, 130 mg/m^2 given every 3 weeks.
Leucovorin
- 200 (mFOLFOX7) or 400 (mFOLFOX6) mg/m^2 given IV every 2 weeks. Part of FOLFOX regimen.
Fluorouracil
- 400 mg/m^2 (IV bolus after leucovorin) and/or 2400 mg/m^2 (continuous infusion over 46 hours). Part of FOLFOX regimen.
Capecitabine
- 1000 mg/m^2 is taken twice per day orally on Days 1-14 of each 3 week cycle. Part of CAPOX regimen.
Pembrolizumab
- 400 mg given by IV on day 1 of cycle 1, then every 6 weeks.

Outcome(s)

Primary Outcome

1A and 1B (Not applicable in Japan):
- Incidence of renal dose-limiting toxicities (DLTs)
1C, 1E, 1F, and 1G:
- Type, incidence, severity, seriousness, and relatedness of adverse events (AEs), including DLTs, and laboratory abnormalities
- Vital signs and other relevant safety variables
1D:
- Type, incidence, severity, seriousness, and relatedness of AEs, including DLTs, and laboratory abnormalities
- Vital signs and other relevant safety variables
- Frequency of dose holds, dose reductions, and discontinuations of tucatinib, trastuzumab, and components of FOLFOX
Phase 2:
- Type, incidence, severity, seriousness, and relatedness of AEs, including DLTs, and laboratory abnormalities
- Vital signs and other relevant safety variables

Secondary Outcome

1A and 1B (Not applicable in Japan):
- Type, incidence, severity, seriousness, and relatedness of adverse events (AEs) and laboratory abnormalities
- Vital signs and other relevant safety variables
- Change in glomerular filtration rate (GFR), as estimated using serum cystatin C, from baseline through 2 cycles of combination therapy
- PK parameters of tucatinib (including but not limited to AUClast, Cmax, Ctrough, and Tmax)
- PK parameters of oxaliplatin (including but not limited to AUClast, Cmax, Tmax)
1C, 1E, 1F, and 1G:
- ORR according to RECIST v1.1 per INV
- DOR (confirmed CR or PR) according to RECIST v1.1 per INV
- PFS according to RECIST v1.1 per INV
- OS
- PK parameters of tucatinib (including but not limited to Ctrough)
Phase 2:
- cORR (confirmed complete response [CR] or partial response [PR]) according to RECIST v1.1 per INV
- DOR (confirmed CR or PR) according to RECIST v1.1 per INV
- PFS according to RECIST v1.1 per INV
- OS

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

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.

Exclude criteria

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)

Related Information

• Primary Sponsor: Mayor JoAl
• Secondary ID(s): NCT04430738