Solid Tumor CancerPhase 1NCT06962254
Imatinib and Trametinib for KRAS-mutated Solid Tumor
A Phase 1 study testing Imatinib and Trametinib in people with Solid Tumor Cancer, run by China Medical University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Solid Tumor Cancer
- What is being tested?
- Imatinib and Trametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteTaiwan
- Study dates
- 10 May 2025to 31 Mar 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
China Medical University Hospital
Taichung, Taichung, 404
Li-Yuan Bai, +886-975-680-928, lybai6@gmail.com
About this study
Official title: Treatment of Solid Tumors Harboring KRAS Mutation With Imatinib and Trametinib
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.
Read the detailed description
KRAS gene mutations are commonly seen in cancers, practically pancreatic cancer, biliary tract cancer, and colorectal cancer. For example, KRAS gene mutations account for about 80% of pancreatic cancers. Clinical studies have found that tumors with KRAS gene mutations have a poor prognosis, inferior response to therapies, and are more likely to develop drug resistance. Therefore, new therapies are necessary for KRAS-mutant patients. Currently, only adagrasib (Krazati) and sotorasib (Lumakras) are approved for patients with KRAS G12C mutations in tumor. Unfortunately, they are ineffective for other KRAS mutations.
The mitogen-activated protein kinase (MEK/ERK) signaling pathway, downstream of KRAS, is hyperactivated in many cancers, making it a promising target for therapy. However, clinical trials targeting this pathway for patients with cancer have failed. Previous research found that a MEK inhibitor trametinib killed KRAS mutant cells but with feedback increased expression of PDGFR, a tyrosine kinase. Thus, the combination of MEK inhibitor with PDGFR inhibitor might be a promising therapeutic strategy.
Investigators have conducted in vivo experiments with two clinically used drugs, imatinib and trametinib, in tumor mouse experiments. The combination of trametinib and the tyrosine kinase inhibitor imatinib showed a good killing effect on pancreatic cancer cells with KRAS gene mutations. For cancers with KRAS non-G12C mutations, the effect of this combination is higher than sotorasib or adagrasib. For pancreatic cancer cells with KRAS G12C mutations, this combination therapy is equivalent to sotorasib or adagrasib alone. Therefore, the combination use of trametinib and imatinib is a potential drug combination that can target pan-KRAS mutant tumors.
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 of the combination of trametinib and imatinib on chemotherapy refractory solid cancers.
- Conditions
- Solid Tumor Cancer
- Being tested
- Imatinib, Trametinib
- Keywords
- KRAS G12D, KRAS G12V, KRAS G12R, MEK/ERK signaling pathway, MEK inhibitor, KRAS G12X, Imatinib, Trametinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Also called Gleevec, Glivec
- 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).
- Preclinical studies have shown that imatinib combined with MEK inhibitors can suppress the growth of KRAS-mutated pancreatic adenocarcinoma.
TrametinibDrug
Also called Mekinist®
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Imatinib; Drug: Trametinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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
- Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the date of registration until the end of treatment, up to 2 years.
Secondary outcomes (4)
Disease control rate
Overall response rate + stable disease
Measured: From the date of registration until disease progression or death, up to 3 years.
Safety profile
The toxicity profiles graded by CTCAE
Measured: From the date of registration until 1 month after disease progression or death, up to 3 years.
Progression-free survival
The time from the date of registration to disease progression or death from any cause.
Measured: From the date of registration until disease progression or death, up to 3 years.
Overall survival
The time from the date of registration to the date of patient's death.
Measured: From the date of registration to the date of patients death, up to 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2025
- Study start10 May 2025 (estimated)
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li-Yuan Bai, China Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06962254
- Sponsor's protocol ID
- CMUH114-REC2-045
- Status last verified
- Apr 2025
- First submitted
- 8 Apr 2025
- Last updated
- 8 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data of this study are available upon reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Solid Tumors Harboring KRAS Mutation With Imatinib and Trametinib
- ClinicalTrials.gov ID
- NCT06962254
- Acronym / sponsor ID
- CMUH114-REC2-045
- Conditions
- Solid Tumor Cancer
- Keywords
- KRAS G12D, KRAS G12V, KRAS G12R, MEK/ERK signaling pathway, MEK inhibitor, KRAS G12X, Imatinib, Trametinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- 10 May 2025 (estimated)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 8 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
KRAS gene mutations are commonly seen in cancers, practically pancreatic cancer, biliary tract cancer, and colorectal cancer. For example, KRAS gene mutations account for about 80% of pancreatic cancers. Clinical studies have found that tumors with KRAS gene mutations have a poor prognosis, inferior response to therapies, and are more likely to develop drug resistance. Therefore, new therapies are necessary for KRAS-mutant patients. Currently, only adagrasib (Krazati) and sotorasib (Lumakras) are approved for patients with KRAS G12C mutations in tumor. Unfortunately, they are ineffective for other KRAS mutations.
The mitogen-activated protein kinase (MEK/ERK) signaling pathway, downstream of KRAS, is hyperactivated in many cancers, making it a promising target for therapy. However, clinical trials targeting this pathway for patients with cancer have failed. Previous research found that a MEK inhibitor trametinib killed KRAS mutant cells but with feedback increased expression of PDGFR, a tyrosine kinase. Thus, the combination of MEK inhibitor with PDGFR inhibitor might be a promising therapeutic strategy.
Investigators have conducted in vivo experiments with two clinically used drugs, imatinib and trametinib, in tumor mouse experiments. The combination of trametinib and the tyrosine kinase inhibitor imatinib showed a good killing effect on pancreatic cancer cells with KRAS gene mutations. For cancers with KRAS non-G12C mutations, the effect of this combination is higher than sotorasib or adagrasib. For pancreatic cancer cells with KRAS G12C mutations, this combination therapy is equivalent to sotorasib or adagrasib alone. Therefore, the combination use of trametinib and imatinib is a potential drug combination that can target pan-KRAS mutant tumors.
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 of the combination of trametinib and imatinib on chemotherapy refractory solid cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib + Trametinib | Experimental | Drug: Imatinib, Drug: Trametinib1. 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. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ImatinibAlso: Gleevec, Glivec1. 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. | Drug | Imatinib + Trametinib |
| TrametinibAlso: Mekinist®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. | Drug | Imatinib + Trametinib |
Primary outcome
Overall response rate (ORR)
Time frame: From the date of registration until the end of treatment, up to 2 years.
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.
4 secondary outcomes
Disease control rate
Time frame: From the date of registration until disease progression or death, up to 3 years.
Safety profile
Time frame: From the date of registration until 1 month after disease progression or death, up to 3 years.
Progression-free survival
Time frame: From the date of registration until disease progression or death, up to 3 years.
Overall survival
Time frame: From the date of registration to the date of patients death, up to 3 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Individual participant dataSharing planned: Yes. The data of this study are available upon reasonable request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imatinib and Trametinib in people with Solid Tumor Cancer, run by China Medical University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Li-Yuan Bai (+886-975-680-928, lybai6@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR) (time frame: From the date of registration until the end of treatment, up to 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2025.