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A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer (MOUNTAINEER-03)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05253651
Recruitment Status : Recruiting
First Posted : February 24, 2022
Last Update Posted : June 11, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.

Brief Summary:

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 test 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.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Drug: tucatinib Drug: trastuzumab Drug: bevacizumab Drug: cetuximab Drug: oxaliplatin Drug: leucovorin Drug: levoleucovorin Drug: fluorouracil Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : October 24, 2022
Estimated Primary Completion Date : August 31, 2025
Estimated Study Completion Date : April 30, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tucatinib Arm
Tucatinib + trastuzumab + mFOLFOX6
Drug: tucatinib
300mg given by mouth (orally) twice daily
Other Name: TUKYSA, ONT-380, ARRY-380

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.
Other Name: Herceptin

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.

Active Comparator: Standard of Care Arm
mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab
Drug: bevacizumab
5mg/kg given by IV every 2 weeks
Other Name: Avastin

Drug: cetuximab
400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly
Other Name: Erbitux

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.




Primary Outcome Measures :
  1. Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 3 years ]
    The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to approximately 6 years ]
    The time from randomization to death from any cause

  2. Confirmed objective response rate (cORR) per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
    The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by BICR

  3. PFS per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
    The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause

  4. cORR per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
    The proportion of participants with confirmed CR or PR according to RECIST v1.1, as assessed by investigators

  5. Duration of response (DOR) per RECIST v1.1 by BICR [ Time Frame: Up to approximately 3 years ]
    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

  6. DOR per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
    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

  7. Time to second progression or death (PFS2) [ Time Frame: Up to approximately 3 years ]
    The time from randomization to disease progression on the next-line of therapy, or death from any cause

  8. Incidence of adverse events (AEs) [ Time Frame: Through 30 days after the last study treatment; approximately 1 year ]
    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.

  9. Incidence of dose alterations [ Time Frame: Through 30 days after the last study treatment; approximately 1 year ]
  10. Trough concentration (Ctrough) [ Time Frame: Approximately 4 months ]
    PK parameter

  11. Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score [ Time Frame: Through 30-37 days after the last study treatment; approximately 1 year ]
    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.

  12. Time to meaningful change in EORTC QLQ30 score [ Time Frame: Through 30-37 days after the last study treatment; approximately 1 year ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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. 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
  • 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

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
  • GI perforation within 12 months of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05253651


Contacts
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Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
Show Show 220 study locations
Sponsors and Collaborators
Seagen Inc.
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Monitor Seagen Inc.
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Responsible Party: Seagen Inc.
ClinicalTrials.gov Identifier: NCT05253651    
Other Study ID Numbers: SGNTUC-029
2021-002672-40 ( EudraCT Number )
First Posted: February 24, 2022    Key Record Dates
Last Update Posted: June 11, 2024
Last Verified: June 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seagen Inc.:
Colorectal Cancer
CRC
Seattle Genetics
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Leucovorin
Bevacizumab
Trastuzumab
Cetuximab
Oxaliplatin
Fluorouracil
Tucatinib
Levoleucovorin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents