NCT03688230撤回2 期
AMELION: A Randomized, Double Blinded, Phase 2, Efficacy and Safety Study of Abituzumab (EMD 525797) in Combination With Cetuximab and FOLFIRI Versus Placebo in Combination With Cetuximab and FOLFIRI in First-line RAS Wild-type, Left-sided, Metastatic Colorectal Cancer Patients With High ανβ6 Integrin Expression.
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of the experimental drug abituzumab (EMD525797) in combination with cetuximab and FOLFIRI in RAS wild-type, left-sided, metastatic colorectal cancer patients with high ανβ6 integrin expression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written informed consent prior to any study specific procedure;
- •Age: ≥18 years;
- •Evidence of newly diagnosed stage IV metastatic colorectal cancer. Primary tumor location on the left side of the Colon (including left splenic flexure) or rectum;
- •Demonstrated wild-type RAS mutation status in the tumor (primary tumor or metastasis) by local assessment;
- •Tumor tissue specimen shows high ανβ6 integrin expression, as determined by central laboratory assessment;
- •Tumor tissue specimen (formalin-fixed, paraffin-embedded block) preferably from primary resection and/or if available from a surgical sample from metastatic site must be available for central laboratory based ανβ6 integrin expression analysis. (No Fine Needle Aspiration [FNA] will be accepted);
- •At least 1 radiographically documented measurable lesion in a previously non-irradiated area according to RECIST (Version 1.1), i.e., this lesion must be adequately measurable in at least 1 dimension (longest diameter to be recorded) as ≥2 cm by conventional techniques or ≥1 cm by spiral CT scan;
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1;
- •Females of childbearing potential must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study;
排除标准
- •Demonstrated any RAS or BRAF mutation;
- •Prior anti-EGFR or other targeted therapy;
- •Prior chemotherapy of the colorectal cancer, except for (neo) adjuvant therapy completed at least 6 months before randomization;
- •Radiotherapy (localized radiotherapy for pain relief is allowed to non-target lesions);
- •Investigational drug treatment for the treatment of malignancies in the past;
- •Concurrent participation in another interventional clinical study;
- •Pregnancy (exclusion confirmed with beta-hCG test) or lactation;
- •Any history or evidence of brain metastases or leptomeningeal metastases;
- •History of secondary malignancy within the past 5 years, except for basal cell carcinoma or carcinoma in situ of the cervix uteri, if treated with curative intent;
- •Concomitant chronic systemic immune or hormone therapy not indicated in this study protocol (except for physiologic replacement; steroids up to 10 mg per day of prednisone equivalent or topical and inhaled steroids are allowed);
- •Clinically relevant coronary artery disease (New York Heart Association [NYHA] functional angina classification III/IV), congestive heart failure (NYHA III/IV), or clinically relevant cardiomyopathy;
- •Uncontrolled hypertension defined as systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg under resting conditions;
- •History of myocardial infarction in the last 12 months, or a high risk of uncontrolled arrhythmia, coagulation disorder associated with bleeding or recurrent thrombotic events, with the exception of arterial fibrillation treated with anti-coagulants;
- •Recent peptic ulcer disease (endoscopically proven) within 6 months of randomization, chronic inflammatory bowel disease, or acute/chronic ileus;
- •Active infection (requiring IV antibiotics and/or antiviral therapy), including active tuberculosis, active or chronic Hepatitis B or C, or ongoing HIV infection, AIDS;
- •Presence of any contra-indications or known hypersensitivity to treatment with abituzumab, cetuximab, and FOLFIRI, or to any of the excipients of these drugs;
- •Concomitant treatment with prohibited medications;
- •Medical or psychological conditions that would not permit the patient to complete the study.
研究组 & 干预措施
Abituzumab + Cetuximab + FOLFIRI
Experimental
Cetuximab:
400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min
- (60 min [± 5 min] after completion of the cetuximab infusion) Abituzumab 1000 mg: every 2 weeks for 60 min
- (60 min [± 5 min] after completion of the abituzumab infusion) FOLFIRI: every 2 weeks Irinotecan 180 mg/m² IV, 30 - 90 min day 1 Folinic acid (racemic) 400 mg/m² IV, 120 min day 1 5-FU 400 mg/m² bolus day 1 5-FU 2400 mg/m² IV over a period of 46 h day 1-2
干预措施: abituzumab (Drug)
Placebo + Cetuximab + FOLFIRI
Placebo Comparator
Cetuximab:
400 mg/m2 over 120 min followed by 250 mg/m2 weekly 60 min or 500 mg/m2 every two weeks, initially 120 min followed by 60 to 90 min
- (60 min [± 5 min] after completion of the cetuximab infusion) Placebo: every 2 weeks for 60 min
- (60 min [± 5 min] after completion of the placebo infusion) FOLFIRI: every 2 weeks Irinotecan 180 mg/m² IV, 30 - 90 min day 1 Folinic acid (racemic) 400 mg/m² IV, 120 min day 1 5-FU 400 mg/m² bolus day 1 5-FU 2400 mg/m² IV over a period of 46 h day 1-2
干预措施: Placebo + Cetuximab + FOLFIRI (Combination Product)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: 16 months
Progression free survival per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator.
次要结局
- Overall Survival (OS)(68 months)
- Objective Response Rate (ORR)(16 months)
- Depth of Response (DPR)(16 months)
- Early Tumor Shrinkage (ETS)(68 months)
- Secondary Resection Rate With a Potentially Curative Intent(16 months)
- Number of participants with treatment-related adverse events summarized by CTCAE severity grade (v5.0).(68 months)
研究者
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