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临床试验/ISRCTN18043777
ISRCTN18043777已完成1 期

A Sequential Phase I study of MEK1/2 inhibitors PD0325901 or Binimetinib combined with c-MET inhibitor PF02341066 in KRAS Mutant and RAS Wild Type (with aberrant c-MET) Colorectal Cancer

niversity of Oxford0 个研究点目标入组 148 人开始时间: 2015年2月4日最近更新:
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适应症

试验速览

阶段
1 期
状态
已完成
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

入排标准

性别
All

入选标准

  • •Participant inclusion criteria as of 21/11/2018:
  • •All patients
  • •1. Age at least 16 years
  • •2. ECOG performance status 0-1
  • •3. Adequate respiratory and cardiac function on clinical assessment
  • •4. Left ventricular ejection fraction (LVEF) = 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
  • •5. Able to give informed consent prior to any screening procedures being performed and be capable of complying with the protocol and its requirements
  • •6. Haematological and biochemical indices within the ranges shown below:
  • •6.1. Haemoglobin (Hb) =9g/dl (transfusion to achieve this allowed),
  • •6.2. Neutrophils= 1,500/µl,
  • •6.3. Platelet count = 100,000/µl,
  • •6.4. AST or ALT =2.5 x ULN, patient with liver metastases <5 x ULN, alkaline phosphatase =5 x ULN,
  • •6.5. Serum Bilirubin =1.5 x ULN,
  • •6.6. Creatinine Clearance =50ml/min
  • •7. Able to swallow oral medication
  • •8. Life expectancy of at least 3 months
  • •Dose escalation phase:
  • •1. Patients with any advanced solid tumours
  • •2. Patients for whom the combination of PF-02341066 with Binimetinib is a reasonable option.
  • •Dose expansion phase:
  • •Patients will be eligible for pre-screening for MErCuRIC provided that:
  • •1. They have given informed consent to screening.
  • •2. They are willing to undergo a biopsy for assessment of tumour RAS mutation status and c-MET assessment.
  • •3. 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:
  • •1. Histologically confirmed colon adenocarcinoma that is either a) RASMT (KRAS codon 12, 13, 61, 117, 146; NRAS codon 12, 13, 61, 117, 146 mutations) or b) RASWT/c-MET mutated or amplified CRC or c) RASWT/c-MET over-expressed with progressive disease on or within 6 months of completion of adjuvant therapy or after chemotherapy and/or targeted therapies for metastatic disease.
  • •2. Prior treatment with an EGFR targeted monoclonal antibody for patients with RASWT/c-MET mutated or amplified CRC or RASWT/c-MET over-expressed.
  • •3. No evidence for a mutation in BRAF at codon600
  • •4. Metastases accessible for biopsy on at least 2-3 occasions
  • •5. At least one other measurable lesion (according to RECIST v1.1).
  • •6. Unsuitable for potential curative resection.
  • •Participant inclusion criteria as of 19/09/2017:
  • •All patients
  • •1. Age at least 16 years
  • •2. ECOG performance status 0-1
  • •3. Adequate respiratory and cardiac function on clinical assessment
  • •4. Left ventricular ejection fraction (LVEF) = 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
  • •5. Able to give informed consent prior to any screening procedures being performed and be capable of complying with the protocol and its requirements
  • •6. Haematological and biochemical indices within the ranges shown below:

排除标准

  • •Exclusion criteria as of 21/11/2018:
  • •1. Unstable ischemic heart disease, cardiac dysrhythmias, coronary/peripheral artery bypass graft or cerebrovascular accident within 6 months prior to starting treatment.
  • •2. Uncontrolled arterial hypertension despite medical treatment.
  • •3. Ongoing congestive heart failure or cardiac dysrhythmias of NCI CTCAE Grade >2 or uncontrolled atrial fibrillation.
  • •4. 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.
  • •5. 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.
  • •6. Patients who have neuromuscular disorders that are associated with elevated CK (e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy);
  • •7. 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.
  • •8. Spinal cord compression unless treated with the patient attaining good pain control and stable or recovered neurologic function.
  • •9. Carcinomatous meningitis or leptomeningeal disease.
  • •10. History of hypoalbuminaemia, or patients with peritoneal disease or pleural disease, where there is a requirement for ascitic or pleural taps.
  • •11. History of retinal vein occlusion, intraocular pressure > 21 mmHg or patient considered at risk of retinal vein thrombosis.
  • •12. History of retinal degenerative disease.
  • •13. History of Gilbert’s syndrome.
  • •14. Active infections (including chronic hepatitis type B or C and HIV infection if status known), severe immunologic defect, compromised bone marrow function
  • •15. Other severe acute or chronic medical conditions
  • •16. Patients who have undergone major surgery = 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure
  • •17. Use of drugs or foods that are known potent CYP3A4 inhibitors or inhibitors or are CYP3A4 substrates with narrow therapeutic indices
  • •18. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous four weeks (six weeks for nitrosoureas, Mitomycin-C)
  • •19. Resting ECG with QTc >480msec at 2 or more time points within a 24h period.
  • •20. Requirement for medication known to prolong QT interval.
  • •21. History of other malignancy less than 3 years before the diagnosis of current cancer
  • •22. Women with the ability to become pregnant (or already pregnant or lactating). However, those fe

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