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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
Recruiting
Conditions
metastatic HER2+breast cancer
Colorectal cancer
D015179
Registration Number
JPRN-jRCT2031220580
Lead Sponsor
Fushimi Chihiro
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
40
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 treatment
-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
-Radiographically measurable disease per RECIST v1.1 with:
- At least one site of disease that iss measureable 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 radiation
-Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
-CNS Inclusion - based on contrast brain magnetic imaging, participants may have any of the following:
- No evidence of brain metastases
- Previouslly treated brain metastates which are asymptomatic

Exclusion Criteria

-Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic setting
- 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
GI perforation within 12 months of enrollment

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Progression-free survival (PFS) by blinded independent central review (BICR) assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Secondary Outcome Measures
NameTimeMethod
Overall survival (OS)<br>Confirmed objective response rate (cORR) by BICR per RECIST v1.1<br>PFS by investigator assessment per RECIST v1.1<br>cORR by investigator assessment per RECIST v1.1<br>Duration of response (DOR) by BICR per RECIST v1.1<br>DOR by investigator assessment per RECIST v1.1<br>Time to second progression or death<br>Incidence of adverse events<br>Incidence of dose alterations<br>Trough concentration<br>Change from baseline in European ORganization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score<br>Time to meaningful change in EORTC QLQC30 score
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