EUCTR2007-005367-10-NL进行中（未招募）不适用
A Phase I/II, open-label, dose escalation trial to evaluate the safety, pharmacokinetics, and pharmacodynamics of RAF265 (CHIR-265) administered orally to patients with locally advanced or metastatic melanoma
适应症
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 211
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
- 性别
- All
入选标准
- •1. Age = 18 years.
- •2. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (for cutaneous melanoma American Joint Committee on Cancer [AJCC] Stage IIIB to IV, pathologic Stage III and IV for noncutaneous melanoma), (see Appendix 1 for the AJCC Staging System for Cutaneous Melanoma).
- •3. Confirmed BRAF mutation status:
- •Phase I: Patients must have either archival tumor tissue or tumor that can be biopsied in order to determine whether it contains mutated or wild-type BRAF. A minimum of 6 patients with tumor accessible to pretreatment and on-treatment biopsies at the MTD will be required before starting the dose expansion (phase II) of the study. The study will retain the option of enrolling patients with tumor that can be biopsied for the purpose of PD assessment at any dose level, if it is needed to inform dose selection for the dose expansion (phase II) or any subsequent study.
- •Phase II: Patients must have documented presence of somatic BRAF mutation in
- •tumor tissue. Acceptable documentation includes:
- •1. Results of mutation analysis performed by Novartis on pre-treatment tumor
- •biopsy tissue or archival tumor tissue received and analyzed during the prescreening
- •Results of mutation analysis documented by a non-Novartis laboratory prior to
- •the study. In this case pre-treatment tumor biopsy tissue or archival tumor tissue
- •should still be sent to Novartis for confirmation of BRAF mutation status and to
- •enable other exploratory analyses to be considered eligible.
- •4. Evidence of measurable disease, defined as at least one lesion that can accurately be measured in at least one dimension as = 20 mm with conventional techniques or = 10 mm with spiral CT scan; cutaneous lesions must have clearly defined margins and measure = 5 mm in at least one diameter.
- •5. Patients scheduled for FDG-PET should have uptake of the tracer in at least one lesion (tumor-to-muscle ratio >2) in the baseline PET/CT scan in order to be eligible for the follow-up FDG PET scans. Patients who do not have uptake will be excluded from having additional FDG-PET scans, but can continue in the trial.
- •6. ECOG Performance Status of 0 or 1.
- •7. Required baseline laboratory data include:
- •Absolute neutrophil count (ANC) = 1,500/mm3 [SI units 109/L];
- •Platelets = 100,000/mm3 [SI units 109/L];
- •Hemoglobin = 9.0 gm/dL [SI units gm/L];
- •Serum creatinine = 1.5 x upper limit of normal (ULN);
- •Bilirubin = 1.5 x ULN;
- •Lipase/Amylase = ULN
- •Aspartate transaminase (AST) = 2.5 x ULN, except for patients with tumor
- •Alanine transaminase (ALT) involvement of the liver who must have AST and ALT = 5 x ULN;
- •8. At least 4 weeks must have elapsed since any major surgery.
- •9. For women of childbearing potential, negative serum pregnancy test within 72 hours of treatment and use of physician-approved method of birth control throughout the study.
- •10. No concurrent anticancer or investigational therapy for at least 4 weeks before study entry, with full recovery (NCI CTCAE Grade 1) from the toxic effects of that treatment.
- •11. Written informed consent, willingness, and ability to comply with all study procedures.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range
排除标准
- •Patients with the following characteristics are excluded:
- •1. Previous therapy with the following molecularly-targeted agents:
- •MEK inhibitors (such as PD0325901)
- •VEGF or VEGFR inhibitors (such as Bevacizumab and small molecule inhibitors with activity against any of the VEGF receptor isoforms)
- •Raf inhibitors (such as sorafenib, PLX4032)
- •2. Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.
- •3. Clinically significant cardiac disease including congestive heart failure (New York Heart Association Class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy; or clinically uncontrolled hypertension (blood pressure > 160/110 mmHg).
- •Impaired cardiac function or clinically significant cardiac diseases, including any one
- •of the following:
- •1. LVEF < 45% as determined by MUGA scan or echocardiogram
- •2. Complete left bundle branch block
- •3. Obligate use of a cardiac pacemaker
- •4. Congenital long QT syndrome
- •5. History or presence of ventricular tachyarrhythmia
- •6. Presence of unstable atrial fibrillation (ventricular response > 100 bpm). Patients
- •with stable atrial fibrillation are eligible, provided they do not meet any of the
- •other exclusion criteria.
- •7. Clinically significant resting bradycardia (< 50 bpm)
- •8. QTc > 480 msec on screening ECG
- •9. Right bundle branch block + left anterior hemiblock (bifasicular block)
- •10. Angina pectoris = 3 months prior to starting study drug
- •11. Acute MI = 3 months prior to starting study drug
- •4. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry, or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
- •5. Active, and uncontrolled clinically significant infection.
- •6. Breastfeeding women.
- •7. Chronic anticoagulation therapy with full strength acetylsalicylic acid (ASA), warfarin sodium, or heparin (low dose ASA = 100 mg, or low dose warfarin = 1 mg to maintain indwelling venous access device patency is allowed).
- •8. History of thromboembolic or cerebrovascular events within the last 12 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.
- •9. History of melena, hematemesis, or hemoptysis within the last 3 months.
- •10. Prior acute or chronic pancreatitis of any etiology.
- •11. Prior intra or extrahepatic biliary obstruction within the previous 12 months, or history of malignant obstruction requiring a biliary stent, unless stably treated with no prior obstruction or blockage of the stent.
- •12. History or current evidence of retinal disease, confirmed by ophtalmologic examination.
- •13.Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
研究者
相似试验
进行中（未招募）
不适用
A phase I/II open label, dose escalation trial to explore the safety and efficacy of ICL670 in patients with iron overload resulting from hereditary hemochromatosis - NDhereditary hemochromatosisMedDRA version: 9.1Level: LLTClassification code 10057873Term: Hereditary haemochromatosisEUCTR2006-002102-57-ITOVARTIS FARMA48
进行中（未招募）
不适用
A phase I/II open label, dose escalation trial to explore the safety and efficacy of ICL670 in patients with iron overload resulting from hereditary hemochromatosisEUCTR2006-002102-57-FRovartis Pharma Services AG48
进行中（未招募）
不适用
A phase I/II open label, dose escalation trial to explore the safety and efficacy of ICL670 in patients with iron overload resulting from hereditary hemochromatosishereditary hemochromatosisMedDRA version: 8.1Level: LLTClassification code 10057874Term: Hereditary hemochromatosisEUCTR2006-002102-57-DEovartis Pharma Services AG48
进行中（未招募）
1 期
ATA-200 gene therapy trial in patients with LGMDR5limb-girdle muscular dystrophy type R5 (previously named LGMD2C)MedDRA version: 20.0Level: PTClassification code: 10028356Term: Muscular dystrophy Class: 100000004850CTIS2023-506440-16-00Atamyo Therapeutics6
进行中（未招募）
不适用
A phase I/II, open-label, dose-escalating study to evaluate the safety, tolerability and pharmacokinetics of twice daily oral midostaurin and to evaluate the preliminary clinical and pharmacodynamic response in pediatric patients with relapsed or refractory leukemia - N/ARelapsed or refractory leukemia in paediatric patientsEUCTR2008-006931-11-SEovartis Pharma Services AG22