Clinical Trials /

Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers

NCT04430738

Description:

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (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).

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Cholangiocarcinoma
  • Colorectal Carcinoma
  • Esophageal Adenocarcinoma
  • Gallbladder Carcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tucatinib Plus Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers
  • Official Title: A Phase 1b/2 Dose Escalation and Expansion Study of Tucatinib in Combination With Trastuzumab and Oxaliplatin-based Chemotherapy for HER2+ Gastrointestinal Cancers

Clinical Trial IDs

  • ORG STUDY ID: SGNTUC-024
  • NCT ID: NCT04430738

Conditions

  • Colorectal Carcinoma
  • Gastric Adenocarcinoma
  • GEJ Adenocarcinoma
  • Esophageal Adenocarcinoma
  • Cholangiocarcinoma
  • Gallbladder Carcinoma

Interventions

DrugSynonymsArms
tucatinibTUKYSACohort 1A
trastuzumabCohort 1A
oxaliplatinCohort 1A
leucovorinCohort 1A
fluorouracilCohort 1A
capecitabineCohort 1C

Purpose

This trial studies tucatinib to find out if it is safe when given with trastuzumab and other anti-cancer drugs (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).

Trial Arms

NameTypeDescriptionInterventions
Cohort 1AExperimentalTucatinib + trastuzumab + FOLFOX given in 14-day cycles
  • tucatinib
  • trastuzumab
  • oxaliplatin
  • leucovorin
  • fluorouracil
Cohort 1BExperimentalTucatinib + trastuzumab + FOLFOX given in 14-day cycles
  • tucatinib
  • trastuzumab
  • oxaliplatin
  • leucovorin
  • fluorouracil
Cohort 1CExperimentalTucatinib + trastuzumab + CAPOX given in 21-day cycles
  • tucatinib
  • trastuzumab
  • oxaliplatin
  • capecitabine
Cohort 2AExperimentalTucatinib + trastuzumab + (FOLFOX or CAPOX)
  • tucatinib
  • trastuzumab
  • oxaliplatin
  • leucovorin
  • fluorouracil
  • capecitabine
Cohort 2BExperimentalTucatinib + trastuzumab + FOLFOX
  • tucatinib
  • trastuzumab
  • oxaliplatin
  • leucovorin
  • fluorouracil

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of renal dose-limiting toxicities (Cohorts 1A, 1B, and 1C)
Time Frame:Up to one month; 2 cycles after receiving all study treatment (each cycle is 14 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events (Cohorts 1A, 1B, and 1C)
Time Frame:Up to approximately 12 months
Safety Issue:
Description:
Measure:Change in glomerular filtration rate from baseline through 2 cycles of combination therapy (Cohorts 1A, 1B, and 1C)
Time Frame:Up to approximately 6 weeks
Safety Issue:
Description:
Measure:Pharmocokinetic (PK) parameter of tucatinib - AUClast (Cohorts 1A, 1B, and 1C)
Time Frame:Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days)
Safety Issue:
Description:
Measure:PK parameter of tucatinib - Cmax (Cohorts 1A, 1B, and 1C)
Time Frame:Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days)
Safety Issue:
Description:
Measure:PK parameter of tucatinib - Ctrough (All cohorts)
Time Frame:Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days)
Safety Issue:
Description:
Measure:PK parameter of tucatinib - Tmax (Cohorts 1A, 1B, and 1C)
Time Frame:Up to approximately 2.5 months; through predose of Cycle 6, Day 1 (each cycle is 14 days)
Safety Issue:
Description:
Measure:PK parameter of oxaliplatin - AUClast (Cohorts 1A, 1B, and 1C)
Time Frame:Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days)
Safety Issue:
Description:
Measure:PK parameter of oxaliplatin - Cmax (Cohorts 1A, 1B, and 1C)
Time Frame:Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days)
Safety Issue:
Description:
Measure:PK parameter of oxaliplatin - Tmax (Cohorts 1A, 1B, and 1C)
Time Frame:Up to 16 days; through Cycle 2, Day 2 (each cycle is 14 days)
Safety Issue:
Description:
Measure:Confirmed objective response rate (cORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 per investigator assessment (INV) (1L gastric, esophogeal, and GEJ Phase 2 cohorts only)
Time Frame:Up to approximately 2.5 years
Safety Issue:
Description:cORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR)
Measure:Duration of response (DOR) according to RECIST v1.1 per INV (Cohort 2A)
Time Frame:Up to approximately 2.5 years
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS) according to RECIST v1.1 per INV (Cohort 2A)
Time Frame:Up to approximately 2.5 years
Safety Issue:
Description: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.
Measure:Overall survival (OS) (Cohort 2A)
Time Frame:Up to approximately 2.5 years
Safety Issue:
Description:OS is defined as the time from treatment initiation to death due to any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seagen Inc.

Trial Keywords

  • HER2+
  • HER2-positive
  • Seattle Genetics

Last Updated

March 2, 2021