Metastatic Colorectal Cancer (CRC)
Conditions
Keywords
Metastatic Colorectal Cancer, RAS Wild-Type, Fruquintinib, Cetuximab-beta, Targeted Therapy
Brief summary
This study aims to evaluate the effectiveness and safety of combining fruquintinib (an oral anti-angiogenesis drug) with cetuximab-beta (an anti-EGFR antibody) in patients with RAS wild-type metastatic colorectal cancer who have already failed at least two lines of standard treatments. Standard therapies for metastatic colorectal cancer often include fluorouracil, oxaliplatin, and irinotecan. However, many patients eventually experience disease progression, and treatment options become limited. Fruquintinib and cetuximab-beta work through different mechanisms: fruquintinib blocks tumor blood vessel growth, while cetuximab-beta blocks EGFR-related cancer cell growth signals. Using these two drugs together may provide additional benefit for patients whose cancer no longer responds to other treatments. This study will enroll 46 patients who meet the eligibility criteria. All participants will take fruquintinib by mouth once daily (3 weeks on and 1 week off) and receive cetuximab-beta by intravenous infusion every 2 weeks. Treatment will continue until the cancer progresses or side effects become intolerable. Doctors will monitor tumor changes every 8 weeks using CT or MRI scans and will also collect blood samples over time to measure circulating tumor DNA (ctDNA), which may help track how the cancer responds to treatment. Safety will be assessed through physical exams, lab tests, and monitoring of side effects. The main goal of the study is to determine the objective response rate (ORR)-how many patients experience measurable tumor shrinkage. Secondary goals include progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety outcomes.
Interventions
DRUGFruquintinib plus Cetuximab-beta
Patients receive fruquintinib 5 mg orally once daily for 3 consecutive weeks followed by 1 week off in a 4-week cycle. Cetuximab-beta is administered intravenously at 500 mg/m² every 2 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Tumor assessments are performed every 8 weeks using RECIST 1.1 criteria. Safety is monitored through physical examinations, laboratory tests, vital signs, ECG, echocardiography, and adverse event reporting. Circulating tumor DNA (ctDNA) is collected at baseline, every 8 weeks during treatment, at progression, and 4-6 weeks after progression to evaluate molecular response and resistance dynamics. The regimen is designed for patients with metastatic colorectal cancer who previously failed standard fluoropyrimidine, oxaliplatin, and irinotecan-based therapies and who have RAS wild-type tumors.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years, inclusive. 2. Fully informed about the study and willing to sign written informed consent. 3. Histologically confirmed metastatic or advanced colorectal adenocarcinoma. 4. Tumor confirmed as NRAS, KRAS, and BRAF wild-type. 5. At least one measurable lesion according to RECIST 1.1 criteria. 6. ECOG performance status of 0-1. 7. Estimated life expectancy ≥ 12 weeks. 8. Prior treatment with oxaliplatin- and irinotecan-based therapy, or failure of at least two prior standard regimens. 9. Prior treatments must have included fluoropyrimidine, oxaliplatin, and irinotecan (with or without bevacizumab or cetuximab). 10. Treatment failure defined as disease progression during therapy or within 3 months after last treatment, or intolerance to toxicity. 11. Recurrence within 6 months after adjuvant/neoadjuvant therapy is considered as first-line failure. 12. Adequate organ function within 7 days prior to enrollment: * ANC ≥ 1.5 × 10⁹/L * Platelets ≥ 80 × 10⁹/L * Hemoglobin ≥ 8 g/dL * Total bilirubin ≤ 1.5 × ULN * AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in liver metastasis) * Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL/min * INR ≤ 1.5 or APTT ≤ 1.5 × ULN 13. No receipt of blood products or growth factors within 14 days prior to enrollment. 14. Able and willing to comply with study procedures and follow-up.
Exclusion criteria
1. Unable or unwilling to comply with the study protocol. 2. Prior treatment with VEGFR tyrosine kinase inhibitors (e.g., regorafenib). 3. Participation in another clinical trial within 4 weeks. 4. Systemic anticancer therapy within 4 weeks before enrollment. 5. Uncontrolled hypertension (SBP \> 140 mmHg or DBP \> 90 mmHg). 6. Any condition that affects drug absorption or inability to take oral medication. 7. Active gastric or duodenal ulcer, ulcerative colitis, or tumor-related active bleeding. 8. Positive fecal occult blood (≥ ++) without endoscopic exclusion of bleeding. 9. Arterial or deep venous thrombosis within 6 months. 10. Significant bleeding within 2 months (melena, hematemesis, hemoptysis). 11. Stroke or transient ischemic attack within 12 months. 12. Significant cardiovascular disease: * Acute myocardial infarction within 6 months * Severe or unstable angina * Heart failure NYHA class \> II * Clinically significant arrhythmia requiring treatment * LVEF \< 50% 13. History of other malignancies within 5 years (except adequately treated in-situ cancers or early non-invasive cancers). 14. Uncontrolled active infection, including HBV or HCV (HBV DNA ≥ 1×10⁴ copies/mL or \>2000 IU/mL). 15. Pregnant or breastfeeding women. 16. Urine protein ≥ 2+ or 24-hour urine protein \> 1.0 g. 17. HIV-positive individuals. 18. Any condition that, in the investigator's judgment, makes the patient unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From the date of first study treatment until documented disease progression, initiation of a new anticancer therapy, or discontinuation of study treatment, whichever occurs first, up to 24 months. | The proportion of patients with a confirmed complete response or partial response using RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From the date of first study treatment to the first documented disease progression or death from any cause, whichever occurs first, up to 24 months. | The time from the date of the first administration of this regimen to the date of first documented disease progression or death due to any cause. |
| Disease Control Rate (DCR) | From the date of first study treatment until documented disease progression, initiation of a new anticancer therapy, or discontinuation of study treatment, whichever occurs first, up to 24 months. | Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1. |
| Overall Survival (OS) | From the date of first study treatment to death from any cause, up to 36 months. | Time from first dose of study treatment until death from any cause. |
| Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events | From the first dose of study treatment through 90 days after the last dose, up to 24 months. | Number and proportion of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Safety assessments include laboratory tests, vital signs, 12-lead electrocardiography, echocardiography, and clinically significant physical examination findings. |
Countries
China
Contacts
CONTACTYongkun Sun
CONTACTQifan Wang
PRINCIPAL_INVESTIGATORYongkun Sun
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed