CRC, Colorectal CancerNCT06985316
An Exploratory Clinical Study Evaluating the Efficacy and Safety of Tunlametinib Combined With Fruquintinib in the Third-line Treatment of Advanced Colorectal Cancer Patients With RAS Mutations.
A study testing Tunlametinib combined with Fruquintinib in people with CRC, Colorectal Cancer, run by Liu Huang.
Trial summary
This study is a prospective, open-label, single-arm clinical study aimed at evaluating the efficacy and safety of Tunlametinib combined with Fruquintinib in the third-line treatment of advanced colorectal cancer patients with RAS mutations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CRC, Colorectal Cancer
- What is being tested?
- Tunlametinib combined with Fruquintinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- No sites listed yet
- Study dates
- 19 May 2025to 27 Apr 2028
- Phase
- Interventional
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1)18 years old or older, both males and females are allowed; 2)ECOG performance status of 0 or 1; 3)Histologically or cytologically proven advanced colorectal cancer; 4)Previous gene testing results indicate positive RAS mutation; 5)According to RECIST v1.1 assessment, there is at least one measurable lesion; 6)Patients who have previously failed second-line systemic antitumor therapy, and have imaging evidence of disease progression, or who are intolerant to the treatment regimen; patients who have failed front line immunotherapy are allowed to receive cross-line treatment; 7)Expected survival period > 3 months; 8)The main organ functions and bone marrow function are normal, meeting the following requirements:
- Blood routine: Hemoglobin ≥80 g/L (no blood transfusion in the last 14 days); Absolute neutrophil count ≥1.5×10^9/L; Platelet count ≥90×10^9/L;
- Liver function: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) ≤2.5×upper limit of normal (ULN); if liver metastasis is present, ALT and AST ≤5×ULN, ALP ≤6×ULN; Total bilirubin ≤1.5×ULN; Albumin ≥30 g/L;
- Kidney function: Serum creatinine ≤1.5×ULN or creatinine clearance calculated by the Cockcroft-Gault formula >60 mL/min;
- Heart function: Echocardiography shows left ventricular ejection fraction (LVEF) ≥55%; ECG QTcF ≤480ms; Creatine kinase (CK) ≤1×ULN, troponin/sensitive troponin ≤1×ULN;
- Coagulation function: International Normalized Ratio (INR) for prothrombin time ≤1.5×ULN; Activated partial thromboplastin time (APTT) ≤1.5×ULN;
- Urinalysis: Urine protein <2; when ≥2, a 24-hour urine protein quantification test should be performed; if the quantification test <1g/24h, they can be included in the group; if urine protein ≥1g/24h, they cannot be included; if urine protein ≥2 without quantification testing, they cannot be included; 9)Able to take oral medication; 10)Women of childbearing age must undergo a pregnancy test (serum or urine) within 14 days prior to enrollment, with negative results, and voluntarily use appropriate contraception during the observation period and for 3 months after the last administration of the study drug; for men, they should be surgically sterilized or agree to use appropriate contraception during the observation period and for 3 months after the last administration of the study drug; 11)Voluntarily participate and sign the informed consent form, expected to have good compliance and be able to cooperate with the study according to the protocol requirements.
Who cannot join
- There are contraindications that influence investigators' choices in the use of therapeutic drugs (according to the latest drug instructions).
- Previously received MEK inhibitors;
- Within 4 weeks before the first use of the drug, underwent major surgery (excluding biopsies and minor outpatient surgeries, such as the placement of vascular access) or experienced serious trauma;
- There is the presence of clinically symptomatic third space effusion (such as large pleural effusion or ascites) that cannot be controlled through drainage or other methods;
- Subjects with symptomatic or untreated brain metastases, leptomeningeal metastases, or spinal cord compression, except for the following conditions: asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain lesions, no need for corticosteroids or antiepileptic drug treatment, and imaging confirms stability of lesions for ≥4 weeks; for patients who have undergone stereotactic brain radiotherapy or surgical treatment, if there has been no disease progression in the brain for 3 months or more, they can be included;
- Impaired cardiac function or clinically significant cardiovascular diseases, including any of the following:
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- Acute coronary syndrome occurring within 6 months prior to treatment initiation, including acute myocardial infarction, unstable angina, coronary artery bypass graft surgery, coronary angioplasty, and stent implantation;
- Symptomatic congestive heart failure (New York Heart Association [NYHA] class ≥ II); evidence of clinically significant arrhythmias and/or conduction abnormalities within 6 months prior to treatment initiation or currently;
- Poorly controlled hypertension (systolic blood pressure ≥ 150 and/or diastolic blood pressure ≥ 100 mmHg under medication control);
- Abnormalities in heart valve morphology recorded by echocardiography (≥ grade 2), Note: Patients with grade 1 heart valve morphology abnormalities (such as mild regurgitation/stenosis) are allowed to enroll, but patients with moderate valve thickening are prohibited from enrolling;
- History of congenital long QT syndrome; or taking medications known to prolong the QT interval and unable to ensure discontinuation during the study.
- A history of retinal diseases during the past or screening, such as: retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal capillary dilatation (Costs disease), retinal pigment epithelial detachment (RPED), etc.; presence of risk factors for RVO during screening (for example, uncontrolled glaucoma or high intraocular pressure, history of hyperviscosity or hypercoagulable syndromes); retinal diseases such as RPED;
- Interstitial lung disease or interstitial pneumonia, including patients with clinically significant radiation pneumonia (i.e., those affecting daily activities or requiring intervention treatment);
- Positive for human immunodeficiency virus (HIV) antibodies, positive for syphilis antibodies (Anti TP), positive for hepatitis C virus (HCV) antibodies and HCV RNA, positive for hepatitis B virus surface antigen (HBsAg) and HBV DNA (positive HBsAg requires further testing for HBV DNA, with HBV DNA ≥ 200 IU/ml or ≥ 10^3 copies/ml);
- A history of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulators or surgery) within 12 months prior to the start of treatment;
- It is known that there is a history of acute or chronic pancreatitis within 6 months before the start of treatment;
- Patients with active gastrointestinal bleeding who require treatment;
- History of allogeneic bone marrow transplantation or organ transplantation;
- Within 2 weeks prior to the initial administration of the drug, there are uncontrolled active infectious diseases (e.g., requiring intravenous administration of antibiotics, antifungals, or antiviral medications), or unexplained fever >38.5°C occurs during the screening period / before the first dose of the drug;
- Incurable electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia detected through blood biochemical tests);
- Past or currently existing neuromuscular diseases related to elevated CK (such as inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy, rhabdomyolysis syndrome);
- Venous or arterial thrombotic events that occurred within the first 6 months prior to the initial use of the drug, such as cerebrovascular accidents (including transient ischemic attacks, intracerebral hemorrhages, cerebral infarctions), deep vein thrombosis, and pulmonary embolism, etc.;
- Symptoms of grade 3 bleeding as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) occurred within 4 weeks prior to the first use of the drug;
- Patients with a history of other malignant tumors in the past 5 years are excluded, except for those who have been completely cured of skin basal cell carcinoma or skin squamous cell carcinoma and cervical carcinoma in situ, and/or any malignant tumor patients who have been cured with no disease or who have been disease-free for at least 5 consecutive years;
- Those who are allergic to any component of this study drug are known;
- A clear history of neurological or psychiatric disorders, including epilepsy and dementia;
- Have received any of the following antitumor treatments prior to the initial study of drug administration (either on the market or in clinical trials): ① Antitumor immunotherapy within 3 weeks; ② Large molecular targeted antitumor therapy such as Bevacizumab within 3 weeks; ③ Chemotherapy or clearly antitumor traditional medicine within 2 weeks; ④ Small molecule targeted antitumor drug treatment within 2 weeks or within 5 half-lives (whichever is longer); ⑤ Subjects who have undergone palliative radiation therapy for bone metastasis within 2 weeks are excluded, but those who have received radiation treatment with an area of ≥30% of the bone marrow within 2 weeks are not allowed to be included;
- Before studying drug administration, all related toxic reactions from antitumor treatments (such as hair loss, skin pigmentation, grade 2 chemotherapy-related peripheral neurotoxicity, grade 2 toxicities caused by immune checkpoint inhibitors like elevated blood sugar or hypothyroidism, etc.) have not recovered to a level of ≤ grade 1 (as determined by NCI CTCAE v5.0);
- Patients may be used in conjunction with other anticancer drugs (bisphosphonates for the treatment of bone metastases are acceptable);
- Uncontrolled comorbidities, including but not limited to severe diabetes (fasting blood glucose > 250 mg/dl or 13.9 mmol/L), or other severe diseases requiring systemic treatment;
- Vaccination with live vaccines or attenuated vaccines within 4 weeks prior to the first dose (Note: If enrolled, participants must not receive live vaccines during the study treatment period and within 30 days after the last dose of the investigational drug);
- For premenopausal female subjects (postmenopausal female patients must have been menopausal for at least 12 months to be considered infertile), a positive pregnancy test result; during the study and at least 30 days after the last administration of the study drug, females of childbearing potential who are hoping to become pregnant, breastfeeding, or unwilling to use effective contraceptive methods (including female partners of male subjects);
- Patients who are undergoing treatment and cannot discontinue intravenous or oral medications that have a prohibitive effect on CYP isoenzymes (strong inducers or strong inhibitors of CYP2C9 and CYP3A4) at least 1 week before starting the study treatment and during the study; patients who are taking medications with a narrow therapeutic window that are metabolized by CYP1A2;
- Inability to swallow capsules or refractory nausea and vomiting, malabsorption, external bile diversion, or any significant small bowel resection that may interfere with the complete absorption of the study drug;
- Researchers believe there are other situations that are not suitable for inclusion. For example, factors related to family or society may affect the safety of the subjects, or the collection of data and samples.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
This study is a prospective, open-label, single-arm clinical study aimed at evaluating the efficacy and safety of Tunlametinib combined with Fruquintinib in the third-line treatment of advanced colorectal cancer patients with RAS mutations.
- Conditions
- CRC, Colorectal Cancer
- Being tested
- Tunlametinib combined with Fruquintinib
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tunlametinib combined with FruquintinibDrug
Tunlametinib combined with Fruquintinib
| Study group | Role | What they receive |
|---|---|---|
| Tunlametinib combined with Fruquintinib | Experimental | Not described Receives: Drug: Tunlametinib combined with Fruquintinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress Free Survival
Time from treatment beginning until disease progression
Measured: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks
Secondary outcomes (6)
Objecitve response rate
Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission
Measured: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Disease control rate
Proportion of patients who achieved a complete response, a partial response, or stable diseas
Measured: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Duration of Response
the time from the initial assessment of CR or PR for subjects with the best tumor efficacy to disease progression or death from any cause.
Measured: Through study completion, an average of 3 weeks
Overall Survival
Time from treatment beginning until death from any cause
Measured: From date of treatment beginning until the date of death from any cause, through study completion, an average of 3 weeks
Incidence of Treatment-related adverse Events
Measured: Through study completion, an average of 3 weeks
Explore therapeutic efficacy biomarkers (including p-ERK levels, etc.)
Measured: Before the subjects start the study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2025
- Study start19 May 2025 (estimated)
- Primary completion27 Apr 2028 (estimated)
- Study completion27 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CRC, Colorectal 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liu Huang
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Liu Huang, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06985316
- Sponsor's protocol ID
- TJ-IRB202504032
- Status last verified
- Mar 2025
- First submitted
- 14 May 2025
- Last updated
- 22 May 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study Evaluating the Efficacy and Safety of Tunlametinib Combined With Fruquintinib in the Third-line Treatment of Advanced Colorectal Cancer Patients With RAS Mutations.
- ClinicalTrials.gov ID
- NCT06985316
- Acronym / sponsor ID
- TJ-IRB202504032
- Conditions
- CRC, Colorectal Cancer
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Liu HuangUniversity, hospital or other
- Study start
- 19 May 2025 (estimated)
- Primary completion
- 27 Apr 2028 (estimated)
- Study completion
- 27 Apr 2028 (estimated)
- First posted
- 22 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.
This study is a prospective, open-label, single-arm clinical study aimed at evaluating the efficacy and safety of Tunlametinib combined with Fruquintinib in the third-line treatment of advanced colorectal cancer patients with RAS mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tunlametinib combined with Fruquintinib | Experimental | Drug: Tunlametinib combined with Fruquintinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 1)18 years old or older, both males and females are allowed; 2)ECOG performance status of 0 or 1; 3)Histologically or cytologically proven advanced colorectal cancer; 4)Previous gene testing results indicate positive RAS mutation; 5)According to RECIST v1.1 assessment, there is at least one measurable lesion; 6)Patients who have previously failed second-line systemic antitumor therapy, and have imaging evidence of disease progression, or who are intolerant to the treatment regimen; patients who have failed front line immunotherapy are allowed to receive cross-line treatment; 7)Expected survival period > 3 months; 8)The main organ functions and bone marrow function are normal, meeting the following requirements:
- Blood routine: Hemoglobin ≥80 g/L (no blood transfusion in the last 14 days); Absolute neutrophil count ≥1.5×10^9/L; Platelet count ≥90×10^9/L;
- Liver function: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) ≤2.5×upper limit of normal (ULN); if liver metastasis is present, ALT and AST ≤5×ULN, ALP ≤6×ULN; Total bilirubin ≤1.5×ULN; Albumin ≥30 g/L;
- Kidney function: Serum creatinine ≤1.5×ULN or creatinine clearance calculated by the Cockcroft-Gault formula >60 mL/min;
- Heart function: Echocardiography shows left ventricular ejection fraction (LVEF) ≥55%; ECG QTcF ≤480ms; Creatine kinase (CK) ≤1×ULN, troponin/sensitive troponin ≤1×ULN;
Key exclusion criteria (35 listed)
- There are contraindications that influence investigators' choices in the use of therapeutic drugs (according to the latest drug instructions).
- Previously received MEK inhibitors;
- Within 4 weeks before the first use of the drug, underwent major surgery (excluding biopsies and minor outpatient surgeries, such as the placement of vascular access) or experienced serious trauma;
- There is the presence of clinically symptomatic third space effusion (such as large pleural effusion or ascites) that cannot be controlled through drainage or other methods;
- Subjects with symptomatic or untreated brain metastases, leptomeningeal metastases, or spinal cord compression, except for the following conditions: asymptomatic brain metastases (i.e., no progressive central nervous system symptoms caused by brain lesions, no need for corticosteroids or antiepileptic drug treatment, and imaging confirms stability of lesions for ≥4 weeks; for patients who have undergone stereotactic brain radiotherapy or surgical treatment, if there has been no disease progression in the brain for 3 months or more, they can be included;
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 |
|---|---|---|
| Tunlametinib combined with FruquintinibTunlametinib combined with Fruquintinib | Drug | Tunlametinib combined with Fruquintinib |
Primary outcome
Progress Free Survival
Time frame: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks
Time from treatment beginning until disease progression
6 secondary outcomes
Objecitve response rate
Time frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Disease control rate
Time frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 6 weeks
Duration of Response
Time frame: Through study completion, an average of 3 weeks
Overall Survival
Time frame: From date of treatment beginning until the date of death from any cause, through study completion, an average of 3 weeks
Incidence of Treatment-related adverse Events
Time frame: Through study completion, an average of 3 weeks
Explore therapeutic efficacy biomarkers (including p-ERK levels, etc.)
Time frame: Before the subjects start the study treatment
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 22 May 2025.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A study testing Tunlametinib combined with Fruquintinib in people with CRC, Colorectal Cancer, run by Liu Huang.
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 7 inclusion and 35 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: opening soon, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
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.
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 Liu Huang (13871312014, huangliu017@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress Free Survival (time frame: Evaluation of tumor burden based on RECIST criteria until first documented progress through study completion, an average of 6 weeks). 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 22 May 2025.