Advanced Colorectal Cancer (Part 1)
Conditions
Brief summary
A New Treatment Opportunity for Patients with Advanced Colorectal Cancer Refractory to Standard Chemotherapy: Clinical Trial of Capecitabine plus Lenvatinib Combination Therapy
Detailed description
This study is for patients with "refractory advanced colorectal cancer" whose tumor has progressed or did not respond to standard, widely used chemotherapies (irinotecan, oxaliplatin, and fluoropyrimidine-based drugs). The purpose of this study is to evaluate the effectiveness and safety of combining Capecitabine (an oral chemotherapy drug) with Lenvatinib (a targeted therapy that blocks blood vessels that help tumors grow)
Interventions
COMBINATION_PRODUCTLenvanib (Lenvatinib),Xeloda (capecitabine)
* Phase I: Lenvatinib dose will be determined using a standard 3+3 dose-escalation design (see table below). * Phase II: Capecitabine 1,000 mg/m² twice daily (BID; administered for 2 weeks followed by 1 week off) in combination with lenvatinib at the dose determined in Phase I, administered once daily (QD), in 3-week cycles.
Sponsors
Seoul National University Bundang Hospital
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* 1\) Voluntarily signed written informed consent 2) Male or female ≥19 years of age 3) Histologically confirmed metastatic or unresectable colorectal adenocarcinoma 4) Metastatic colorectal cancer refractory to irinotecan, oxaliplatin, and fluoropyrimidines 5) ECOG performance status 0, 1, or 2 6) Measurable lesion per RECIST v1.1 7) Hemoglobin ≥9.0 g/dL, ANC ≥1,500/μL, Platelets ≥100,000/μL, Serum creatinine \<1.5×ULN, AST/ALT \<3×ULN, Total bilirubin \<1.5×ULN (all without transfusion or G-CSF within 14 days of screening) 8) Able to understand and comply with the study protocol through completion 9) Women of childbearing potential: negative pregnancy test within 14 days before first dose; agreement to use adequate contraception for ≥6 months after last dose 10) Men with pregnant or potentially pregnant partners: agreement to use adequate contraception (e.g., condom) for ≥3 months after last dose
Exclusion criteria
* 1\) Pregnant or breastfeeding women 2) History of another malignancy within the past 5 years (except papillary or follicular thyroid cancer) 3) Uncontrolled infection or other systemic diseases 4) Known hypersensitivity to the investigational drugs 5) Presence of bowel stent or biliary stent with risk of perforation or bleeding 6) Esophageal/gastric varices or other risk of gastrointestinal hemorrhage 7) Presence of significant uncontrolled concurrent illness or recent medical condition, including but not limited to: * Significant cardiovascular disorder: congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction, or cerebrovascular accident within 6 months prior to the first dose; or history of cardiac arrhythmia requiring treatment at screening. * Uncontrolled hypertension (systolic BP \>150 mmHg or diastolic BP \>90 mmHg) despite optimized antihypertensive therapy. * Thromboembolic disorder or significant risk of severe hemorrhage. The degree of tumor invasion of major blood vessels (e.g., carotid artery) must be considered due to the potential risk of serious hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy. 8\) Uncontrolled proteinuria (3+ or higher on spot urinalysis; 2+ acceptable only if U/PCR ≤1 g/Cr) 9) QTcF \>480 msec 10) Known DPD (dihydropyrimidine dehydrogenase) deficiency 11) Active CNS metastases and/or carcinomatous meningitis 12) Judged ineligible by the investigator 13) Major surgery within 1 month prior to enrollment 14) Receipt of another investigational drug within 4 weeks prior to enrollment or currently enrolled in another clinical trial 15) Requiring concurrent systemic anticancer therapy during the study 16) Currently receiving prohibited concomitant medications (e.g., sorivudine and analogues, allopurinol) that cannot be discontinued before first dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Efficacy Analysis | rom the first dose of study treatment until documented disease progression, treatment discontinuation, withdrawal of consent, death, or end of study, with tumor response assessed every 6 weeks, up to 48 months. | Outcome Measure Title: Objective Response Rate (ORR) per RECIST v1.1 Outcome Measure Description: Objective Response Rate (ORR) is defined as the proportion of treated patients who achieve a best overall response of complete response (CR) or partial response (PR), as assessed according to RECIST v1.1. Tumor response will be evaluated using CT or MRI every 6 weeks. The best overall response will be determined from the start of study treatment until disease progression, treatment discontinuation, death, or end of study. ORR will be summarized with a 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | baseline until disease progression or death from any cause, assessed up to 24 months | The proportion of all patients achieving complete response , partial response , or stable disease will be calculated and presented with a 95% confidence interval. |
| Quality of Life Assessment | QoL assessed at baseline and every 6 weeks during treatment, up to a maximum of 24 months. | QoL will be assessed using the FACT-G7 questionnaire. To compare score changes between baseline and post-treatment time points: * If data satisfy normality: paired t-test will be used. * If data do not satisfy normality: Wilcoxon signed-rank test will be used. QoL changes will be presented as descriptive statistics showing the score change from baseline at each time point. A Linear Mixed Model (LMM) or Repeated Measures ANOVA will be used to statistically test the trend of score changes over time. Item-level missing data Prorating per the FACT-G7 Scoring will be applied. In general, if ≥50% of items comprising a subscale are answered, the missing items will be imputed by the mean score of the answered items. Visit-level missing data Primary analysis will be based on patients with available data at both baseline and the assessment time point. To characterize the pattern and cause of missing data, the questionnaire compliance rate at each time point will be reported as statistics. |
| Overall Survival | From the first dose of study treatment until death from any cause, assessed up to 48 months. | Overall Survival (OS) is defined as the time from the first dose of study treatment to death from any cause. OS will be analyzed using the Kaplan-Meier method and reported in months. |
Countries
South Korea
Outcome results
None listed