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临床试验/EUCTR2014-000463-40-IE
EUCTR2014-000463-40-IE进行中（未招募）1 期

A Sequential Phase I study of MEK1/2 inhibitors PD-0325901 or Binimetinib combined with cMET inhibitor Crizotinib in RAS Mutant and RAS Wild Type(with aberrant c-MET) Colorectal Cancer - MErCuRIC1: MEK and MET Inhibition i

niversity of Oxford0 个研究点目标入组 148 人开始时间: 2016年5月10日最近更新:
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试验速览

阶段
1 期
状态
进行中（未招募）
入组人数
148
研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型
Interventional clinical trial of medicinal product

入排标准

入选标准

  • •All patients
  • •Age = 16 years
  • •ECOG performance status 0-1 (Appendix 1)
  • •Adequate respiratory function on clinical assessment
  • •Left ventricular ejection fraction (LVEF)= 50% as determined by a multigated
  • •acquisition (MUGA) scan or echocardiogram
  • •Able to give informed consent prior to any screening procedures being
  • •performed and be capable of complying with the protocol and its requirements
  • •Haematological and biochemical indices within the ranges shown below:
  • •- Haemoglobin (Hb) =9g/dl (transfusion to achieve this allowed),
  • •- Neutrophils= 1,500/µl,
  • •- Platelet count = 100,000/µl,
  • •- AST or ALT = 2.5 x ULN, patient with liver metastases = 5 x ULN, Alkaline phosphatase = 5 x ULN
  • •- Serum Bilirubin = 1.5 x ULN
  • •- Creatinine Clearance = 50ml/min (calculated by Cockcroft Gault equation, or by EDTA) (Appendix 2)
  • •Able to swallow oral medication
  • •Life expectancy of at least 3 months
  • •Dose escalation phase (combination of PF-02341066 with PD-0325901):
  • •Patients with any advanced solid tumours
  • •Patients for whom PF-02341066 with PD-0325901 is a reasonable option.
  • •Dose escalation phase (combination of PF-02341066 with Binimetinib):
  • •Patients with any advanced solid tumours
  • •Patients for whom PF-02341066 with Binimetinib is a reasonable option.
  • •Dose expansion
  • •Patients will be eligible for pre-screening for MErCuRIC provided that:
  • •They have given informed consent to screening.
  • •They are willing to undergo a biopsy for assessment of tumour RAS mutation status and c-MET assessment.
  • •The Investigator anticipates that they are likely to satisfy the eligibility criteria for the trial. Formal screening should not
  • •be performed until the tumour pre-screening result is known.
  • •Eligibility for the trial, in patients passing pre-screening, requires:
  • •Histologically confirmed colorectal adenocarcinoma that is either a) RASMT (KRAS codon 12, 13, 61,117, 146; NRAS codon 12, 13, 62, 227, 146 mutations) or b) RASWT/c-MET mutated or amplified or c) RASWT/c-MET over-expressed with progressive disease on or within 6 months of completion of adjuvant therapy or after chemotherapy/targeted therapies for metastatic disease.
  • •Prior treatment with an EGFR targeted monoclonal antibody for patients with RASWT/c-MET mutated or amplified CRC or RASWT/c-MET over-expressed CRC.
  • •No evidence for a mutation in BRAF at codon600.
  • •Metastases accessible for biopsy on 2-3 occasions.
  • •At least one other measurable lesion (according to RECIST v1.1).
  • •Unsuitable for potential curative resection.
  • •Are the trial subjects under 18? yes
  • •Number of subjects for this age range: 1
  • •F.1.2 Adults (18-64 years) yes
  • •F.1.2.1 Number of subjects for this age range 90
  • •F.1.3 Elderly (>=65 years) yes
  • •F.1.3.1 Number of subjects for this age range 50

排除标准

  • •All patients
  • •Unstable ischaemic heart disease, cardiac dysrhythmias, coronary/peripheral artery bypass graft or cerebrovascular
  • •accident within 6 months prior to starting treatment.
  • •Uncontrolled arterial hypertension despite medical treatment.
  • •Ongoing congestive heart failure or cardiac dysrhythmias of NCI CTCAE Grade =2 or uncontrolled atrial fibrillation.
  • •History of extensive disseminated/bilateral or known presence of Grade 3 or 4 interstitial fibrosis or interstitial lung
  • •disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung
  • •disease (ILD), obliterative bronchiolitis, and pulmonary fibrosis. A history of prior radiation pneumonitis is allowed.
  • •Any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions)
  • •and/or leptomeningeal metastases. However, patients treated with stereotactic radiotherapy or surgery are eligible if
  • •the patient remained without evidence of CNS disease progression = 3 months. Patients must be off corticosteroid
  • •therapy for = 3 weeks .
  • •Patients who have neuromuscular disorders that are associated with elevated CK (e.g., inflammatory myopathies,
  • •muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy);
  • •Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment.
  • •NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels
  • •should be avoided while on Binimetinib treatment.
  • •Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered
  • •neurologic function.
  • •Carcinomatous meningitis or leptomeningeal disease.
  • •History of hypoalbuminaemia, or patients with peritoneal disease or pleural disease, where there is a requirement
  • •for ascitic or pleural taps.
  • •History of retinal vein occlusion, intraocular pressure > 21 mmHg or patient considered at risk of retinal vein
  • •thrombosis (e.g. history of hyperviscosity or hypercoagulability syndromes).
  • •History of retinal degenerative disease.
  • •History of Gilbert’s syndrome.
  • •Active infections (including chronic hepatitis type B or C and HIV infection if status known), severe immunologic
  • •defect, compromised bone marrow function
  • •Other severe acute or chronic medical conditions
  • •Patients who have undergone major surgery = 3 weeks prior to starting study drug or who have not recovered from
  • •side effects of such procedure
  • •Use of drugs or foods that are known potent CYP3A4 inhibitors or inhibitors or are CYP3A4 substrates with narrow
  • •therapeutic indices
  • •Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous
  • •four weeks (six weeks for nitrosoureas, Mitomycin-C)
  • •Resting ECG with QTc >480msec at 2 or more time points within a 24h

研究者

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