Fruquintinib Plus Anti-EGFR Antibody for Third-Line Treatment of RAS Wild-Type mCRC

Официальное название

A Phase II Study of Fruquintinib Combined With Anti-EGFR Monoclonal Antibody in Third-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer

Обзор

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.

Вмешательства

• Препарат Fruquintinib 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

Первичные конечные точки

• Objective Response Rate (ORR) [Срок оценки: 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.]

Вторичные конечные точки (4)

• Progression-Free Survival (PFS) [Срок оценки: 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.]
• Disease Control Rate (DCR) [Срок оценки: 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.]
• Overall Survival (OS) [Срок оценки: From the date of first study treatment to death from any cause, up to 36 months.]
• Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events [Срок оценки: From the first dose of study treatment through 90 days after the last dose, up to 24 months.]

Критерии участия

Критерии включения

• Age 18-75 years, inclusive.
• Fully informed about the study and willing to sign written informed consent.
• Histologically confirmed metastatic or advanced colorectal adenocarcinoma.
• Tumor confirmed as NRAS, KRAS, and BRAF wild-type.
• At least one measurable lesion according to RECIST 1.1 criteria.
• ECOG performance status of 0-1.
• Estimated life expectancy ≥ 12 weeks.
• Prior treatment with oxaliplatin- and irinotecan-based therapy, or failure of at least two prior standard regimens.
• Prior treatments must have included fluoropyrimidine, oxaliplatin, and irinotecan (with or without bevacizumab or cetuximab).
• Treatment failure defined as disease progression during therapy or within 3 months after last treatment, or intolerance to toxicity.
• Recurrence within 6 months after adjuvant/neoadjuvant therapy is considered as first-line failure.
• 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
• No receipt of blood products or growth factors within 14 days prior to enrollment.
• Able and willing to comply with study procedures and follow-up.

Критерии исключения

• Unable or unwilling to comply with the study protocol.
• Prior treatment with VEGFR tyrosine kinase inhibitors (e.g., regorafenib).
• Participation in another clinical trial within 4 weeks.
• Systemic anticancer therapy within 4 weeks before enrollment.
• Uncontrolled hypertension (SBP > 140 mmHg or DBP > 90 mmHg).
• Any condition that affects drug absorption or inability to take oral medication.
• Active gastric or duodenal ulcer, ulcerative colitis, or tumor-related active bleeding.
• Positive fecal occult blood (≥ ++) without endoscopic exclusion of bleeding.
• Arterial or deep venous thrombosis within 6 months.
• Significant bleeding within 2 months (melena, hematemesis, hemoptysis).
• Stroke or transient ischemic attack within 12 months.
• 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%
• History of other malignancies within 5 years (except adequately treated in-situ cancers or early non-invasive cancers).
• Uncontrolled active infection, including HBV or HCV (HBV DNA ≥ 1×10⁴ copies/mL or >2000 IU/mL).
• Pregnant or breastfeeding women.
• Urine protein ≥ 2+ or 24-hour urine protein > 1.0 g.
• HIV-positive individuals.
• Any condition that, in the investigator's judgment, makes the patient unsuitable for the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences and Peking U — Пекин

Идентификаторы

NCT: NCT07724223 · NCCH0046

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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