Clinical Trial Evaluating the Efficacy of Capecitabine Plus Lenvatinib in Patients With Advanced Colorectal Cancer Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidine

Official title

A Phase I/II Clinical Trial Evaluating the Efficacy of Capecitabine Plus Lenvatinib in Patients With Advanced Colorectal Cancer Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidine

Overview

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 product Lenvanib (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.

Primary outcome measures

• Primary Efficacy Analysis [Time frame: 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.]

Secondary outcome measures (3)

• Disease Control Rate [Time frame: baseline until disease progression or death from any cause, assessed up to 24 months]
• Quality of Life Assessment [Time frame: QoL assessed at baseline and every 6 weeks during treatment, up to a maximum of 24 months.]
• Overall Survival [Time frame: From the first dose of study treatment until death from any cause, assessed up to 48 months.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• 172, Dolma-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, Korea Seoul National University Bunda — Seongnam-si

Identifiers

NCT: NCT07683949 · LENCAP-CRC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗