Recruiting NCT06997497

A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)

Phase III Interventional Colon Adenocarcinoma Rectal Adenocarcinoma

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Calderasib, Oxaliplatin, Leucovorin/levofolinate calcium, 5-Fluorouracil.
Who it may be relevant to: Registry conditions: Colon Adenocarcinoma, Rectal Adenocarcinoma. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Brazil, Canada +24
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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)

Overview

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.

Interventions

Drug Calderasib
Oral tablet
Drug Oxaliplatin
Per label
Drug Leucovorin/levofolinate calcium
Per label
Drug 5-Fluorouracil
Per label
Biological Cetuximab
Per label
Drug Bevacizumab
Per label
Drug Bevacizumab biosimilar
Per label

Primary outcome measures

Number of Participants Experiencing Dose-Limiting Toxicity (DLT) [Time frame: Up to approximately 28 days]
Part 1: Number of Participants Who Experience an Adverse Event (AE) [Time frame: Up to approximately 44 months]
Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE [Time frame: Up to approximately 44 months]
Progression Free Survival (PFS) [Time frame: Up to approximately 44 months]

Secondary outcome measures (12)

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]

Eligibility criteria

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

Has a histologically confirmed diagnosis of locally advanced unresectable or metastatic (unresectable Stage III or Stage IV as defined by American Joint Committee on Cancer \[AJCC\] eighth edition) colorectal adenocarcinoma
Part 2 only: Has not received systemic anticancer therapy for locally advanced unresectable or metastatic colorectal cancer; an exception is permitted for 1-2 cycles of FOLFOX or 1 cycle of CAPOX as optional chemotherapy before or during the screening period
Demonstrates presence of a Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation
Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load
Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Exclusion criteria

The main exclusion criteria include but are not limited to the following:

Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea)
Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
Has known partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency
HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization, with the exception of the optional chemotherapy
Has 1 or more conditions that, in the opinion of the investigator, make the participant ineligible for treatment with bevacizumab
Has known additional malignancy that is progressing or has required active treatment within the past 3 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease
Has active infection requiring systemic therapy
Has not adequately recovered from major surgery or have ongoing surgical complications
Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Single blind
Primary purpose: Treatment

Study locations

China · 34 centers

Anhui Provincial Cancer Hospital ( Site 0803) — Hefei
The Second Affiliated Hospital of Anhui Medical University ( Site 0813) — Hefei
Peking Union Medical College Hospital ( Site 0824) — Beijing
Peking University First Hospital(Daxing Area) ( Site 0838) — Beijing
Chongqing University Cancer Hospital ( Site 0808) — Chongqing
Chongqing University Three Gorges Hospital ( Site 0837) — Wanzhou
Fujian Cancer Hospital ( Site 0807) — Fuzhou
The First Affiliated Hospital of Xiamen University ( Site 0806) — Xiamen
… and 26 more centers

United States · 32 centers

Los Angeles Hematology Oncology Medical Group ( Site 0084) — Los Angeles
UCLA Hematology/Oncology - Santa Monica ( Site 0088) — Santa Monica
University of Colorado Health - Harmony-Cancer Care and Hematology - Ft. Collins ( Site 00 — Fort Collins
Rocky Mountain Cancer Centers (RMCC) ( Site 8000) — Lone Tree
Florida Cancer Specialists - South ( Site 7002) — Fort Myers
Orlando Health Cancer Institute ( Site 0065) — Orlando
Florida Cancer Specialists - North ( Site 7001) — St. Petersburg
Florida Cancer Specialists - East ( Site 7000) — West Palm Beach
… and 24 more centers

Japan · 16 centers