Cholangiocarcinoma Clinical Trial
Official title:
A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy or Pembrolizumab-containing Combinations for HER2+ Gastrointestinal Cancers
This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (pembrolizumab, FOLFOX, and CAPOX). It will look at what side effects happen when participants take this combination of drugs. A side effect is anything the drug does other than treating cancer. It will also look at whether tucatinib works with these drugs to treat certain types of cancer. The participants in this trial have HER2-positive (HER2+) cancer in their gut, stomach, intestines, or gallbladder (gastrointestinal cancer).
Status | Recruiting |
Enrollment | 40 |
Est. completion date | October 31, 2025 |
Est. primary completion date | March 31, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 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 - Participants must be candidates to receive an oxaliplatin-based regimen as part of their standard-of-care treatment for all cohorts, except Cohort 1G. - HER2+ disease, as determined by historic or local laboratory testing - 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 - Eastern Cooperative Oncology Group Performance Status score of 0 or 1. Exclusion Criteria: - History of known hypersensitivity to planned study treatment - Known to be positive for Hepatitis B or C - 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) There are additional inclusion criteria. The study center will determine if criteria for participations are met. |
Country | Name | City | State |
---|---|---|---|
Japan | National Cancer Center Hospital | Chuo-ku | Other |
Japan | National Cancer Center Hospital East | Kashiwa-shi | Other |
Japan | St. Marianna University School of Medicine | Kawasaki-shi | Other |
Japan | The Cancer Institute Hospital of Japanese Foundation for Cancer Research | Koto-ku | Other |
Japan | Aichi Cancer Center | Nagoya-shi | Other |
Japan | Osaka International Cancer Institute | Osaka | Other |
Japan | Kindai University Hospital | Osakasayama-Shi | Other |
United States | New Mexico Cancer Center | Albuquerque | New Mexico |
United States | University of Colorado Hospital / University of Colorado | Aurora | Colorado |
United States | Gabrail Cancer Center Research, LLC | Canton | Ohio |
United States | Levine Cancer Institute | Charlotte | North Carolina |
United States | University of Chicago Medical Center | Chicago | Illinois |
United States | Cleveland Clinic, The | Cleveland | Ohio |
United States | Duke University Medical Center | Durham | North Carolina |
United States | SCL Health Good Samaritan Medical Center Cancer Centers of Colorado | Lafayette | Colorado |
United States | Stanford Cancer Center / Blood and Marrow Transplant Program | Palo Alto | California |
United States | Mayo Clinic Arizona | Phoenix | Arizona |
United States | Mayo Clinic Rochester | Rochester | Minnesota |
United States | Washington University in St Louis | Saint Louis | Missouri |
United States | Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington | Seattle | Washington |
United States | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida |
United States | Johns Hopkins Medical Center | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Seagen Inc. |
United States, Japan,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Incidence of renal dose-limiting toxicities (DLTs) (Cohorts 1A and 1B) | Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days) | ||
Primary | Incidence of adverse events (AEs) (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B) | An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Up to approximately 12 months | |
Primary | Incidence of laboratory abnormalities (Cohorts 1C, 1D, 1E, 1F, 1G, 2A, and 2B) | Up to approximately 12 months | ||
Primary | Incidence of DLTs (Cohorts 1C, 1D, 1E, 1F, and 1G) | Up to approximately 12 months | ||
Primary | Incidence of dose alterations (Cohort 1D) | Up to approximately 12 months | ||
Secondary | Incidence of AEs (Cohorts 1A and 1B) | An AE is defined as any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Up to approximately 12 months | |
Secondary | Incidence of laboratory abnormalities (Cohorts 1A and 1B) | Up to approximately 12 months | ||
Secondary | Change in glomerular filtration rate (GFR) from baseline through 2 cycles of combination therapy (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to approximately 6 weeks | |
Secondary | Pharmacokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days) | |
Secondary | PK parameter of tucatinib - Cmax (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days) | |
Secondary | PK parameter of tucatinib - Ctrough (Cohorts 1A, 1B, 1C, 1E, 1F, and 1G) | To be summarized using descriptive statistics | Up to approximately 2.5 months; through predose of Cycle 6, Day 1 | |
Secondary | PK parameter of tucatinib - Tmax (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to approximately 2.5 months; through predose of Cycle 2, Day 1 (each cycle is 14 days) | |
Secondary | PK parameter of oxaliplatin - AUClast (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days) | |
Secondary | PK parameter of oxaliplatin - Cmax (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days) | |
Secondary | PK parameter of oxaliplatin - Tmax (Cohorts 1A and 1B) | To be summarized using descriptive statistics | Up to 15 days; through Cycle 2, Day 1 (each cycle is 14 days) | |
Secondary | Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (Cohort 2A) | cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) | Up to approximately 2.5 years | |
Secondary | Duration of response (DOR) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A) | 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 or death from any cause, whichever occurs first. | Up to approximately 2.5 years | |
Secondary | Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohorts 1C, 1E, 1F, 1G, and 2A) | PFS is defined as the time from the date of treatment initiation to the date of disease progression or death from any cause, which occurs first. | Up to approximately 2.5 years | |
Secondary | Overall survival (OS) (Cohort 1C, 1E, 1F, 1G, and 2A) | OS is defined as the time from treatment initiation to death due to any cause | Up to approximately 2.5 years | |
Secondary | Objective response rate (ORR) (Cohorts 1C, 1E, 1F, and 1G) | ORR is defined as the proportion of subjects with confirmed CR or PR, according to RECIST v1.1. | Up to approximately 2.5 years |
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