Fruquintinib Plus Anti-EGFR Antibody for Third-Line Treatment of RAS Wild-Type mCRC
A Phase II Study of Fruquintinib Combined With Anti-EGFR Monoclonal Antibody in Third-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer
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.
調査の概要
研究の種類
介入
入学 (推定)
46
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Yongkun Sun
- 電話番号：(+86)010-87788800
- メール：hsunyk@cicams.ac.cn
研究連絡先のバックアップ
- 名前：Qifan Wang
- 電話番号：(+86)010-87788800
- メール：wqf10028@163.com
研究場所
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-
Beijing Municipality
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Beijing、Beijing Municipality、中国、100021
- 募集
- National Cancer Center / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
-
コンタクト：
- Yongkun Sun
- 電話番号：(+86)010-87788800
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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 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.
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective Response Rate (ORR)
時間枠：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.
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The proportion of patients with a confirmed complete response or partial response using RECIST 1.1
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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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression-Free Survival (PFS)
時間枠：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.
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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.
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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.
|
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Disease Control Rate (DCR)
時間枠：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.
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Proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1.
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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.
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Overall Survival (OS)
時間枠：From the date of first study treatment to death from any cause, up to 36 months.
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Time from first dose of study treatment until death from any cause.
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From the date of first study treatment to death from any cause, up to 36 months.
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Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events
時間枠：From the first dose of study treatment through 90 days after the last dose, up to 24 months.
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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.
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From the first dose of study treatment through 90 days after the last dose, up to 24 months.
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Circulating Tumor DNA (ctDNA)
時間枠：At baseline, every 8 weeks during study treatment, at documented disease progression, and 4-6 weeks after progression, up to 24 months after the first dose.
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Quantitative and qualitative changes in ctDNA levels at baseline, during treatment, at progression, and 4-6 weeks post-progression to evaluate molecular response and resistance patterns.
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At baseline, every 8 weeks during study treatment, at documented disease progression, and 4-6 weeks after progression, up to 24 months after the first dose.
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Yongkun Sun、National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2026年1月16日
一次修了 (推定)
2028年10月1日
研究の完了 (推定)
2029年1月31日
試験登録日
最初に提出
2026年7月14日
QC基準を満たした最初の提出物
2026年7月23日
最初の投稿 (実際)
2026年7月24日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月24日
QC基準を満たした最後の更新が送信されました
2026年7月23日
最終確認日
2026年1月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。