Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line Treatment (MINOAS)
A Open Label, Non Randomized, Phase Two Trial in Metastatic Colorectal Cancer (mCRC) With the Combination of m FOLFIRI Plus Aflibercept as First Line Treatment: MINOAS Trial
調査の概要
詳細な説明
Colorectal cancer accounts for 8% of all malignant tumors in adults and is considered as a major cause of cancer morbidity and mortality worldwide. Although curative surgical resection is possible in 70-80% of patients at diagnosis, almost half of them will develop local or/and metastatic recurrence and will die of the disease with the liver been the most common site of metastatic spread from CRC.
Combinations of infusional administrated 5-fluorouracil/Leucovorin with irinotecan or oxaliplatin are accepted as the mainstay of first-line treatment and have increase the median overall survival of patients with advanced CRC from 12 months to about 21-22 months. In addition, resection for colorectal metastases (mainly in the liver), has become the standard of care, for patients with limited metastatic disease confounded to the liver and currently remains the only potentially curative therapy Aflibercept, also known as vascular endothelial growth factor (VEGF) Trap, is an angiogenesis inhibitor with a unique mechanism of action. Aflibercept is a recombinant fusion protein that consists of portions of human VEGFR1 and VEGFR2 extracellular domains fused to the Fc portion of human immunoglobulin G1. This fusion protein binds all forms of Vascular Endothelial Growth Factor-A, as well as VEGF-B and placental growth factor, additional angiogenic growth factors that appear to play a role in tumor angiogenesis and inflammation. Aflibercept has been shown to bind VEGF-A, VEGF-B, and placental growth factor (PlGF) with higher affinity than their native receptors. In vitro and in vivo studies have shown that aflibercept can inhibit new vessel growth and tumor vascularization in tumor models.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Athens、ギリシャ
- 251 Air Forces Military Hospital of Athens
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Athens、ギリシャ
- Anicancer Hospital of Athens "Agios Savvas"
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Athens、ギリシャ
- Anticanscer Hospital of Athens "Agios Savvas"
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Athens、ギリシャ
- Athens Hospital "Mitera" Hygia Polis
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Athens、ギリシャ
- General Hospital of Athens "Aretaieio"
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Athens、ギリシャ
- General Hospital of Athens "Sotiria"
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Athens、ギリシャ
- IASO general hospital
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Río、ギリシャ
- University Hospital of Patras-Rio
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Thessaloniki、ギリシャ
- Thessaloniki Bioclinic
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Crete
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Heraklion、Crete、ギリシャ、71110
- University Hospital of Heraklion Crete
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Patients with histologically documented adenocarcinomas of colon or rectum with unresectable metastatic disease.
- No prior treatment for metastatic disease
- Metastatic liver disease assessable with diffusion-weighted Magnetic Resonance Imaging (MRI)
- No previous treatment with bevacizumab or Cetuximab or Panitumumab.
- Patients may have receive fluoropyrimidines with or without oxaliplatin as adjuvant treatment, if they have progressed > 12 months after the end of the last cycle of the adjuvant treatment
- Performance Status (ECOG) 0-2
- Life expectancy ≥ 3 months.
- Effective contraception for both male and female subjects if the risk of conception exists.
- Adequate laboratory parameters: Absolute neutrophils count ≥ 1.5 x 109 /L, Platelets ≥ 100 x 109 /L, Leucocytes > 3,000/mm; Hemoglobin> 10.5g/dl, creatinine clearance ≥ 60 ml/min, Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour, Magnesium ≥ lower limit of normal, Calcium ≥ lower limit of normal, total Bilirubin ≤ 1.5 times the upper limit of normal; aspartate and alanine aminotransferase ≤ 3 times of the upper normal limit in absence of liver metastases, or ≤5x Upper Normal Limits (UNL) in presence of liver metastases, alkaline phosphatases < 5x UNL
- All patients will have to sign written informed consent in order to participate in the study.
- Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial
Exclusion Criteria:
- Known hypersensitivity reaction to the component of the treatment.
- Inability to underwent a diffusion-weighted MR Imaging at baseline and in predefined time points
- Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
- History or evidence upon physical examination of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
- Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
- Treatment with any other investigational medicinal product within 28 days prior to study entry.
- Other serious and uncontrolled non-malignant disease
- Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
- Gilbert's syndrome
- Intolerance to atropine sulfate or loperamide
- Known dihydropyrimidine dehydrogenase deficiency
- Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization
- Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis
- Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
- INR in absence of anticoagulation therapy > 1.25 or poorly controlled anti-coagulation therapy on coumadin or heparin compounds (INR >3.0)
- History of myocardial infarction and/or stroke within 6 months prior to randomization, New York Heart Association (NYHA) class III and IV congestive heart failure
- History of life threatening (grade 4) venous thromboembolic events (including pulmonary embolism) within 6 months prior to registration,
- Bowel obstruction
- Legal incapacity or limited legal capacity.
- Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent.
- A second primary tumour other than non-melanoma skin cancer or in situ cervical cancer.
- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on chest CT scan.
研究計画
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 |
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実験的:FOLFIRI/Aflibercept
5 Fluorouracil/Leucovorin/Irinotecan/Aflibercept
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5 Fluorouracil: 400mg/m2, bolus infusion in <5min followed by 5 Fluorouracil: 2400mg/m2, i.v in 46 hours continuous infusion (cycle repeated every two weeks)
他の名前:
Leucovorin: 400mg/m2, i.v in 2 hours infusion (cycle repeated every two weeks)
他の名前:
Irinotecan: 180mg/m2, i.v in 90min infusion (cycle repeated every two weeks)
他の名前:
Aflibercept: 4mg/kg i.v in 1 hour infusion (cycle repeated every two weeks)
他の名前:
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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 |
時間枠 |
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全体の回答率
時間枠:8週目の疾患評価
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8週目の疾患評価
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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全生存
時間枠:1年
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1年
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無増悪サバイバル
時間枠:1年
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1年
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Toxicity profile (CTCAE v4.0)
時間枠:Every 2 weeks up to 100 weeks
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From date of randomization until the date of last follow up or death from any cause, assessed up to 100 weeks
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Every 2 weeks up to 100 weeks
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協力者と研究者
捜査官
- 主任研究者:John Souglakos, MD、Hellenic Oncology Research Group
- 主任研究者:Athanasios Kotsakis, MD、Hellenic Oncology Research Group
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CT/14.01
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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。
転移性結腸直腸がんの臨床試験
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5 Fluorouracilの臨床試験
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Encube Ethicals Pvt. Ltd.CBCC Global Research完了
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National Institute of Public Health, CambodiaEmory University; World Vision International; World Vision, Hong Kong; World Vision, Cambodia完了
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U.S. Army Medical Research and Development Command募集
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Suzhou Kintor Pharmaceutical Inc,Suzhou Koshine Biomedica, Inc.積極的、募集していない