A Phase 3, Randomized, Open-label, Multicenter Clinical Study to Evaluate the Safety and Efficacy of MK-1084, Cetuximab, and mFOLFOX6 Versus mFOLFOX6 With or Without Bevacizumab as First-line Treatment of Participants With KRAS G12C-mutant, Locally Advanced Unresectable or Metastatic Colorectal Cancer (KANDLELIT-012)
Summary
Researchers are looking for other ways to treat locally advanced or metastatic colorectal cancer (mCRC) that is unresectable and has a gene mutation called KRAS G12C. Standard (or usual) treatments for this type of colorectal cancer may include mFOLFOX6 with or without bevacizumab. Researchers want to learn if adding calderasib (the study medicine) and cetuximab to mFOLFOX6 can treat locally advanced or mCRC with the KRAS G12C mutation. Calderasib and cetuximab are targeted therapies. The goals of this study are to learn: * About the safety of calderasib with cetuximab and mFOLFOX6 and if people tolerate the treatments * If people who receive calderasib with cetuximab and mFOLFOX6 live longer without mCRC growing or spreading compared to people who receive mFOLFOX6 with or without bevacizumab.
Detailed description
This study will have 2 parts.
Arms & interventions
- DrugCalderasib
Oral tablet
- DrugOxaliplatin
Per label
- DrugLeucovorin/levofolinate calcium
Per label
- Drug5-Fluorouracil
Per label
- BiologicalCetuximab
Per label
- DrugBevacizumab
Per label
- DrugBevacizumab biosimilar
Per label
Outcome measures
Primary
Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration.
Time frame: Up to approximately 28 days
Part 1: Number of Participants Who Experience an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to approximately 44 months
Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to approximately 44 months
Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first.
Time frame: Up to approximately 44 months
Secondary
Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
Overall Survival (OS)
Time frame: Up to approximately 5 years
Duration of Response (DOR)
Time frame: Up to approximately 4 years
Part 2: Number of Participants with an Adverse Event (AE)
Time frame: Up to approximately 5 years
Part 2: Number of Participants who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 5 years
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
Time frame: Baseline and up to approximately 5 years
Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score
Time frame: Baseline and up to approximately 5 years
Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score
Time frame: Baseline and up to approximately 5 years
Change from Baseline in the EORTC-QLQ-C30 Appetite Loss (Item 13) Score
Time frame: Baseline and up to approximately 5 years
Change from Baseline in the EORTC-Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
Time frame: Baseline and up to approximately 5 years
Time to First Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
Time frame: Baseline and up to approximately 5 years
TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
Time frame: Baseline and up to approximately 5 years
TTD in EORTC QLQ-C30 Role Functioning (Items 6 and 7) Score
Time frame: Baseline and up to approximately 5 years
TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score
Time frame: Baseline and up to approximately 5 years
TTD in EORTC QLQ-CR29 Bloating (Item 37) Score
Time frame: Baseline and up to approximately 5 years
Eligibility criteria
Study locations (27)
Los Angeles Hematology Oncology Medical Group ( Site 0084)
Los Angeles, California, 90017
University of Colorado Health - Harmony-Cancer Care and Hematology - Ft. Collins ( Site 0087)
Fort Collins, Colorado, 80528
Rocky Mountain Cancer Centers (RMCC) ( Site 8000)
Lone Tree, Colorado, 80124
Florida Cancer Specialists - South ( Site 7002)
Fort Myers, Florida, 33901
Orlando Health Cancer Institute ( Site 0065)
Orlando, Florida, 32806
Florida Cancer Specialists - North ( Site 7001)
St. Petersburg, Florida, 33705
Florida Cancer Specialists - East ( Site 7000)
West Palm Beach, Florida, 33401
University of Iowa ( Site 0074)
Iowa City, Iowa, 52242
University of Kentucky ( Site 0055)
Lexington, Kentucky, 40536
Norton Cancer Institute, Audubon Hospital Campus ( Site 0054)
Louisville, Kentucky, 40217
Greater Baltimore Medical Center ( Site 0068)
Baltimore, Maryland, 21204
Hattiesburg Clinic ( Site 0064)
Hattiesburg, Mississippi, 39401
Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana ( Site 2000)
Billings, Montana, 59102
University Of Nebraska Medical Center ( Site 0078)
Omaha, Nebraska, 68198
Renown Regional Medical Center ( Site 0056)
Reno, Nevada, 89502
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0060)
Hackensack, New Jersey, 07601
San Juan Oncology Associates, P.C ( Site 2011)
Farmington, New Mexico, 87401
Ellis Hospital ( Site 0098)
Schenectady, New York, 12308
Miami Valley Hospital South ( Site 0075)
Centerville, Ohio, 45459
Texas Oncology - DFW ( Site 8002)
Dallas, Texas, 75246
UT Southwestern Medical Center ( Site 0059)
Dallas, Texas, 75390
Texas Oncology - Northeast Texas ( Site 8001)
Denison, Texas, 75020
Texas Oncology - San Antonio ( Site 8004)
San Antonio, Texas, 78240
Community Cancer Trials of Utah ( Site 0086)
Ogden, Utah, 84405
University of Virginia ( Site 0080)
Charlottesville, Virginia, 22908
Virginia Cancer Specialists, PC ( Site 0069)
Fairfax, Virginia, 22031
Fred Hutchinson Cancer Center ( Site 0076)
Seattle, Washington, 98109