A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer
A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer
This study is being done to find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also determine what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.
Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).
Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:
* mFOLFOX6 alone,
* mFOLFOX6 with bevacizumab, or
* mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.
Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).
Participants will be assigned randomly to the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:
* mFOLFOX6 alone,
* mFOLFOX6 with bevacizumab, or
* mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.
Not Available
Phase III
Adults
Not Available
Not Available
Not Available
International
Vanderbilt University
04-03-2024
Eligibility
18 Years and older
ALL
false
Inclusion Criteria:
Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
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
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.
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.
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 radiation
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 radiation
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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
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
Exclusion Criteria:
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 enrollment
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 enrollment
Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
Previous treatment with anti-HER2 therapy
Previous treatment with anti-HER2 therapy
Ongoing Grade 3 or higher neuropathy
Ongoing Grade 3 or higher neuropathy
Active or untreated gastrointestinal (GI) perforation at the time of screening.
Active or untreated gastrointestinal (GI) perforation at the time of screening.
Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic
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
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.
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.
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 radiation
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 radiation
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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
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
Exclusion Criteria:
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 enrollment
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 enrollment
Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
Previous treatment with anti-HER2 therapy
Previous treatment with anti-HER2 therapy
Ongoing Grade 3 or higher neuropathy
Ongoing Grade 3 or higher neuropathy
Active or untreated gastrointestinal (GI) perforation at the time of screening.
Active or untreated gastrointestinal (GI) perforation at the time of screening.
