Clinical trial: Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers (NCT04430738)

Eligibility criteria:
Inclusion Criteria:

          -  Participants must have unresectable or metastatic solid malignancy that is
             histologically or cytologically confirmed to be one of the tumor types listed below:

               -  CRC

               -  Gastric adenocarcinoma

               -  GEJ adenocarcinoma

               -  Esophageal adenocarcinoma

               -  Cholangiocarcinoma

               -  Gallbladder carcinoma

          -  Participants must be candidates to receive an oxaliplatin-based regimen as part of
             their standard-of-care treatment.

          -  Participants in phase 1b cohorts or in Cohort 2B can be receiving an oxaliplatin-based
             regimen

               -  For phase 1b cohorts utilizing FOLFOX: up to 2 cycles of FOLFOX (≤85 mg/m2
                  oxaliplatin per 2-week cycle) may have been received prior to Cycle 1 Day 1 of
                  study treatment

               -  For phase 1b cohorts utilizing CAPOX: up to 2 cycles of FOLFOX (≤85 mg/m2
                  oxaliplatin per 2-week cycle) or one cycle of CAPOX (≤130 mg/m2 oxaliplatin per
                  3-week cycle) may have been received prior to Cycle 1 Day 1 of study treatment.

               -  For all phase 1b cohorts: if subject has received oxaliplatin in prior cycles at
                  higher doses than those listed above, there must be a minimum of 28 days off
                  treatment prior to Cycle 1 Day 1 of treatment in this study.

               -  For Cohort 2B prior to the first dose of study treatment:

                    -  Subjects may have received up to 1 cycle of FOLFOX (≤85 mg/m2 oxaliplatin
                       per 2-week cycle) prior to Cycle 1 Day 1 but may not have received prior
                       oxaliplatin for metastatic disease

                    -  Oxaliplatin received in an adjuvant setting is permitted if >6 months prior
                       to Cycle 1 Day 1

                    -  At least 21 days must have elapsed from prior systemic anticancer therapy
                       (including hormonal and biologic therapy but excluding 1 cycle of FOLFOX),
                       non-central nervous system radiation, and treatment with other experimental
                       agents

          -  HER2+ disease, as determined by laboratory testing based on one of the following:

               -  For CRC, cholangiocarcinoma, and gallbladder carcinoma:

                    -  HER2 amplification or overexpression from fresh or archival tumor tissue
                       utilizing one of the following Clinical Laboratory Improvement Amendments
                       (CLIA) certified or International Organization for Standardization (ISO)
                       tests:

                         -  HER2 overexpression (3+ immunohistochemistry [IHC])

                         -  HER2 (ERBB2) amplification by in situ hybridization assay (fluorescence
                            in situ hybridization [FISH] or chromogenic in situ hybridization
                            signal ratio ≥2.0 or gene copy number >6)

                         -  HER2 (ERBB2) amplification by next generation sequencing (NGS) assay

                    -  HER2 amplification in a CLIA certified blood-based NGS assay

               -  Gastric, GEJ, and esophageal adenocarcinomas must use the following criteria:

                    -  HER2+ overexpression (IHC3+) by an FDA approved assay, from a newly obtained
                       biopsy or surgical specimen, evaluated following the package insert's
                       interpretational manual for gastric adenocarcinoma. IHC2+ is eligible if the
                       tumor is HER2 amplified by an FDA approved in situ hybridization assay

          -  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 oxaliplatin, fluoropyrimidines, leucovorin,
             trastuzumab, or compounds chemically or biologically similar to tucatinib, except for
             Grade 1 or 2 infusion related reactions to oxaliplatin or trastuzumab that were
             successfully managed, or known allergy to any of the excipients in the study drugs

          -  Treatment with oxaliplatin dose in excess of the limitations specified in the
             inclusion criteria

        There are additional inclusion criteria. The study center will determine if criteria for
        participations are met.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 63-year-old man comes to the clinic for recent unintentional weight loss. The patient also has epigastric discomfort after meals. He has no known medical problems and takes no medications. His blood pressure is 130/75 and pulse rate is 88/min. He is not febrile. Upper endoscopy shows a lesion in the stomach that shows typical features of diffuse-type adenocarcinoma presenting with signet ring cells that do not form glands.

Patient description (patient's own words): I went to the clinic because I had been losing so much weight that it was concerning. I'm a 63-year-old guy, and it is something rather unusual. I'm always suffering from stomachache after every meal. I've never been sick, and I don't take any medicine. The doctor took my blood pressure and told me it was 130/75, and my pulse rate was 88/min. I'm not febrile! I also had to do an endoscopy, and they found a lesion in my stomach that shows typical features of stomach cancer. I'm totally devastated...

Does the patient match the trial criteria? Entailment