Imatinib and Trametinib for KRAS-mutated Solid Tumor

NCT06962254 | Recruiting Phase 1

• 1 other identifier: CMUH114-REC2-045
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

In this pilot trial, participants with unresectable solid cancers harboring KRAS mutations will be provided with a compassionate treatment if their diseases progress after current standard treatments, or there is no available standard treatment. This trial will evaluate the efficacy and safety of the combination of trametinib and imatinib on chemotherapy refractory solid cancers.

Conditions

Solid Tumor Cancer

Keywords

KRAS G12D; KRAS G12V; KRAS G12R; MEK/ERK signaling pathway; MEK inhibitor; KRAS G12X; Imatinib; Trametinib

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Overall response is evaluated using Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). A participant is considered to have responded if either of the following outcomes is achieved: 1. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm 2. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From the date of registration until the end of treatment, up to 2 years.

Secondary Outcomes (4)

• Disease control rate

  From the date of registration until disease progression or death, up to 3 years.

• Safety profile

  From the date of registration until 1 month after disease progression or death, up to 3 years.

• Progression-free survival

  From the date of registration until disease progression or death, up to 3 years.

• Overall survival

  From the date of registration to the date of patients death, up to 3 years.

Study Arms (1)

Imatinib + Trametinib

EXPERIMENTAL

1. Participants will receive oral imatinib 100 mg/day and trametinib 2 mg/day. 2. If there is no severe adverse event, the dose of imatinib could be increased to 200mg/day and the dose of trametinib reduced to 1 mg/day since cycle 2 per treating physician's judgement. 3. Four weeks of treatment is regarded as one cycle.

Drug: Imatinib; Drug: Trametinib

Interventions

Imatinib DRUG

1. Imatinib is binding to the ATP-binding site of BCR-ABL, blocking its activity and preventing uncontrolled proliferation to target the BCR-ABL fusion protein in chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It also inhibits PDGFR and c-KIT receptors, suppressing tumor growth and angiogenesis in gastrointestinal stromal tumors (GIST). 2. Preclinical studies have shown that imatinib combined with MEK inhibitors can suppress the growth of KRAS-mutated pancreatic adenocarcinoma.

Also known as: Gleevec, Glivec

Imatinib + Trametinib

Trametinib DRUG

Trametinib inhibits the MEK1 and MEK2 enzymes, preventing the downstream phosphorylation and activation of ERK1/2, which are crucial for the RAS-RAF-MEK-ERK signaling pathway. By blocking this pathway, trametinib reduces cell proliferation and induces apoptosis in tumor cells harboring pathway mutations.

Also known as: Mekinist®

Imatinib + Trametinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included in the study if they meet all of the following criteria:
• Participants with age ≥ 20 years old.
• Histologically confirmed locally advanced or metastatic solid tumors with KRAS G12X mutation.
• Documented disease progression during or within 6 months after standard chemotherapies or no available standard therapy.
• Documented measurable disease as defined by RECIST v1.1.
• ECOG Performance Status 0-2.
• Participants has life expectancy of at least 8 weeks.
• Adequate hematologic parameters, and hepatic and renal functions defined as
• Hematological: white blood cell ≥3,000/ul, absolute neutrophil count (ANC) ≥1,500/ul, hemoglobin ≥9 g/dl and platelet count ≥ 90,000/ul.
• Hepatic: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥2.5 x upper limit of normal (ULN) (≥5.0 x ULN if attributable to liver metastases), and total bilirubin ≥1.5 x upper limit of normal (ULN) (≥3.0 x ULN if attributable to liver metastases).
• Renal: serum creatinine level ≦2 x ULN or creatinine clearance ≥ 30 ml/min \[calculated by either Cockcroft-Gault equation \[(140-age) x body weight (kg) x (1 if male or 0.85 if female) / (72 x serum creatinine level, mg/dl)\] or 24-hour urine test\].
• Adequate blood coagulation function, defined as prothrombin time international normalized ratio (PT INR)≦ 2.3.
• Normal ECG or ECG without any clinical significant findings.
• Able to understand and sign an informed consent (or have a legal representative who is able to do so).
• Women or men of reproductive potential should agree to use an effective contraceptive method.

You may not qualify if:

• The participants will be excluded from the study if they meet any of the following criteria:
• History of allergic reaction to trametinib or imatinib.
• Participant who has been exposed to KRAS G12C inhibitors.
• Participant who has been exposed or currently taking kinase inhibitors.
• Participants who have major abdominal surgery, radiotherapy or other, investigating agents within 2 weeks. Patients who have palliative radiotherapy will be eligible if the irradiated area does not involve the only lesion of measurable / evaluable disease.
• Participants with liver cirrhosis with Child-Pugh score ≥ 8 (Late Child-Pugh B and Child-Pugh C).
• Participants with electrolyte abnormalities that have not been corrected.
• Participants with metastatic lesion in central nervous system.
• Participants with active infection.
• Subjects who have not recovered adequately from any toxicity from other anti- cancer treatment regimens and/or complications from major surgery prior to starting therapy.
• Participants who have serious concomitant systemic disorders incompatible with the study, i.e. poorly controlled diabetes mellitus, auto-immune disorders, or other conditions that in the opinion of the investigator would preclude the subject's participation in the study.
• Participants who have other prior or concurrent malignancy except for adequately treated in situ carcinoma or basal cell carcinoma of skin, or any malignancy which remains disease-free for 3 or more years after curative treatment.
• Females who are breastfeeding or pregnant at screening or baseline.
• Participants with psychiatric illness which would preclude study compliance.
• Participants taking strong CYP450 enzyme system inducers (rifampicin, glucocorticoids, phenobarbital and pentobarbital) or inhibitors (ketoconazole, cimetidine, erythromycin, verapamil, diltiazem and cyclosporine), and other unapproved drugs.

Sponsors & Collaborators

• China Medical University Hospital: lead

Study Sites (1)

China Medical University Hospital

Taichung, Taichung, 404, Taiwan

RECRUITING

MeSH Terms

Interventions

Imatinib Mesylate; trametinib

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Central Study Contacts

Li-Yuan Bai

CONTACT

+886-975-680-928; lybai6@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Hematology and Oncology

Study Record Dates

• First Submitted: April 8, 2025
• First Posted: May 8, 2025
• Study Start: May 10, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: May 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: From the beginning of study to 1 years after completion of study.
• Access Criteria: The data of this study are available from the principle investigator upon reasonable request.

Locations

TW (1)