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Clinical Trial Details

Geo Regions

Category

Gastrointestinal Cancer

Tucatinib

An Open-label Randomized Phase 3 Study of Tucatinib in Combination With Trastuzumab and mFOLFOX6 Versus mFOLFOX6 Given With or Without Either Cetuximab or Bevacizumab as First-line Treatment for Subjects With HER2+ Metastatic Colorectal Cancer
Phase 3
NCT05253651

Active enrolling

Globe
Locations

United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Slovakia, Spain, Switzerland, Taiwan, United Kingdom

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Study design

Participant Group/Arm

EXPERIMENTAL: Tucatinib Arm

Tucatinib + trastuzumab + mFOLFOX6

Intervention/Treatment

DRUG: tucatinib

300mg given by mouth (orally) twice daily

DRUG: trastuzumab

8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.

DRUG: oxaliplatin

85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

DRUG: leucovorin

400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

DRUG: levoleucovorin

200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

DRUG: fluorouracil

400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.
Participant Group/Arm

ACTIVE_COMPARATOR: Standard of Care Arm

mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab

Intervention/Treatment

DRUG: bevacizumab

5mg/kg given by IV every 2 weeks

DRUG: cetuximab

400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

DRUG: oxaliplatin

85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

DRUG: leucovorin

400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

DRUG: levoleucovorin

200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

DRUG: fluorouracil

400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.
Study design table for Clinical Trial

Key eligibility criteria

Inclusion criteria
  • Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
  • Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory
    • If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatme
  • HER2+ disease as determined by a tissue based assay performed at a central laboratory.
  • Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date.
  • Radiographically measurable disease per RECIST v1.1 with:
    • At least one site of disease that is measurable and that has not been previously irradiated, or
    • If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiati
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:
    • No evidence of brain metastases
    • Previously treated brain metastases which are asymptomatic
  • Prior systemic anticancer therapy for colorectal cancer (CRC) in the locally advanced unresectable or metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.
    • Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed \>6 months prior to enrollme
  • Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
  • Previous treatment with anti-HER2 therapy
  • Ongoing Grade 3 or higher neuropathy
  • Active or untreated gastrointestinal (GI) perforation at the time of screening.
Exclusion criteria
  • Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization.
    • Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment
  • Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
  • Previous treatment with anti-HER2 therapy
  • Ongoing Grade 3 or higher neuropathy
  • Active or untreated gastrointestinal (GI) perforation at the time of screening

Key dates

Study start date
  • October 2022
Estimated primary completion date
  • April 2028

Key endpoints

Primary Outcome Measures
Outcome Measure

Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR)

Measure Description

The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause

Time Frame

Up to approximately 3 years

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

Overall survival (OS)

Measure Description

The time from randomization to death from any cause

Time Frame

Up to approximately 6 years

Outcome Measure

Confirmed objective response rate (cORR) per RECIST v1.1 by BICR

Measure Description

The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by BICR

Time Frame

Up to approximately 3 years

Outcome Measure

PFS per RECIST v1.1 by investigator assessment

Measure Description

The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause

Time Frame

Up to approximately 3 years

Outcome Measure

cORR per RECIST v1.1 by investigator assessment

Measure Description

The proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators

Time Frame

Up to approximately 3 years

Outcome Measure

Duration of response (DOR) per RECIST v1.1 by BICR

Measure Description

The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause

Time Frame

Up to approximately 3 years

Outcome Measure

DOR per RECIST v1.1 by investigator assessment

Measure Description

The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause

Time Frame

Up to approximately 3 years

Outcome Measure

Time to second progression or death (PFS2)

Measure Description

The time from randomization to disease progression on the next-line of therapy, or death from any cause

Time Frame

Up to approximately 3 years

Outcome Measure

Incidence of adverse events (AEs)

Measure Description

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.

Time Frame

Through 30 days after the last study treatment; approximately 1 year

Outcome Measure

Incidence of dose alterations

Measure Description

Time Frame

Through 30 days after the last study treatment; approximately 1 year

Outcome Measure

Trough concentration (Ctrough)

Measure Description

PK parameter

Time Frame

Approximately 4 months

Outcome Measure

Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score

Measure Description

Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/quality of life (QoL) scales, higher scores indicate better functioning or global health status/quality of life (QoL). For symptom scales, higher scores indicate greater symptom burden.

Time Frame

Through 30-37 days after the last study treatment; approximately 1 year

Outcome Measure

Time to meaningful change in EORTC QLQ30 score

Measure Description

The time from baseline to the first onset of a ≥10-point changes in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores. Scale scores range from 0-100. For functioning and global health status/QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.

Time Frame

Through 30-37 days after the last study treatment; approximately 1 year

Secondary Outcome Measures table for Clinical Trial

Number of participants

400

Collaborators and investigators

Sponsor: Seagen Inc.

Collaborator: None

This information is current as of August 6th 2024.
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More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT05253651