EUCTR2013-003596-35-GB进行中（未招募）1 期
An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor Trametinib in Children and Adolescents Subjects with Cancer or Plexiform Neurofibromas and Trametinib in Combination with Dabrafenib in Children and Adolescents with Cancers Harboring V600 mutation.
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 145
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. Written informed consent – a signed informed consent and/or assent (as age appropriate) for study participation including pharmacokinetics sampling will be obtained according to institutional guidelines;
- •2. Male or female between one month and < 18 years of age (inclusive) at the time of signing the informed consent form
- •3. Part C and Part D subjects between 12 months and < 18 years of age, inclusive
- •4. Part A subjects < 2 years of age will not be included in the initial dose escalation
- •5. Must have a disease that is relapsed/refractory to all potentially curative standard treatment regimens or must have a current disease for which there is no known curative therapy, or therapy proven to prolong survival with an acceptable quality of life.
- •6. Prior therapy: The subject’s disease (i.e. cancer, NF-1 with PN, or LCH) must have relapsed after or failed to respond to frontline curative therapy or there must not be other potentially curative treatment options available. Curative therapy may include surgery, radiation therapy, chemotherapy, or any combination of these modalities. Subjects must have recovered to grade =1 from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment.
- •7. Performance score of =50% according to the Karnofsky / Lansky performance status scale.
- •8. Females of child-bearing potential must be willing to practice acceptable methods of birth control. Additionally, females of childbearing potential must have a negative serum pregnancy test within 7 days prior to start of study drugs;
- •9. In France, subjects will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
- •10.10. Must have adequate multi organ function as defined by the following
- •values: renal function - 24 hr creatinine clearance (revised Schwartz
- •formula), or radioisotope glomerular filtration rate (GFR) >=60 milliliter
- •(mL) per minute per 1.73 meter square (mL/min/1.73m^2); or a serum
- •creatinine <=upper limit of normal (ULN) for age and gender; liver
- •functions as bilirubin (sum of conjugated + unconjugated) <=1.5 x ULN
- •for age, alanine aminotransferase (ALT) <=2.5 x ULN; for the purposes
- •of enrollment and toxicity monitoring the ULN for ALT will be 45 unit per
- •liter (U/L); cardiac function - corrected QT (QTcB) interval <480
- •milliseconds (msec), left ventricular ejection fraction (LVEF) >=lower
- •limit of normal (LLN) by ECHO.
- •Able to swallow and retain enterally (per oral [PO] or nasogastric or
- •gastric tube) administered medication and does not have any clinically
- •significant gastrointestinal abnormalities that may alter absorption such
- •as malabsorption syndrome or major resection of the stomach or bowels.
- •Adequate Blood Pressure Control defined as: Blood pressure <= the
- •95th percentile for age, height, and gender.
- •Other protocol-defined inclusion criteria, including some for each part,
- •Are the trial subjects under 18? yes
- •Number of subjects for this age range: 145
- •F.1.2 Adults (18-64 years) no
- •F.1.2.1 Number of subjects for this age range
- •F.1.3 Elderly (>=65 years) no
- •F.1.3.1 Number of subjects for this age range
排除标准
- •1. Lactating or pregnant female.
- •2. History of another malignancy including resected non-melanomatous skin cancer
- •3. Subjects with Neurofibromatosis Type-1 (NF-1) associated optic pathway tumors are excluded if they are actively receiving therapy for the optic pathway tumor or do not meet criteria for Plexiform Neurofibroma or malignant solid tumor
- •4. Subjects with a history of NF-1 related cerebral vascular anomaly (such as Moyamoya)
- •5. Subjects with NF-1 actively receiving therapy for the optic pathway tumour
- •6. Subjects with NF-1 and only Plexiform Neurofibroma (PN) lesions that cannot be evaluated by volumetric analysis
- •7. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures
- •8. Any prohibited medication(s) as described in Section 9.2.
- •9. Any medications for treatment of left ventricular systolic dysfunction
- •10. Part B cohorts 1, 2 and 3: Previous treatment with dabrafenib, trametinib or another MEK inhibitor (exception: prior treatment with sorafenib is permitted).
- •Patients who have had prior dabrafenib therapy may enroll into cohort B4.
- •Patients who have had prior dabrafenib therapy and had benefit from that therapy as determined by the investigator, are allowed in Part C or Part D
- •11. Administration of an investigational study treatment within 30 days preceding the first dose of study treatment(s) in this study
- •12. Have a known hypersensitivity reaction or idiosyncrasy to drugs chemically related to study treatment or excipients that contraindicate their participation
- •13. Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, or liver metastases)
- •14. History of hepatic sinusoid obstructive syndrome (Venoocculsive disease) within the prior 3 months
- •15. History of heparin-induced thrombocytopenia
- •16. History of interstitial lung disease or pneumonitis
- •17. History or current evidence of retinal vein occlusion (RVO)
- •18. For subjects with solid tumors that are not primary central nervous system (CNS) tumors or NF-1 associated plexiform neurofibromas, subjects with symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression are excluded
- •19. A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
- •20. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events Grade 2 or higher from previous anti-cancer therapy, except alopecia
- •21. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the Medical Lead for guidance to enrol the subject
- •22. A history or evidence of cardiovascular risk including: a QT interval
- •corrected for heart rate using the Bazett's formula (QTcB) >=480 msec;
- •a history or evidence of current clinically significant uncontrolled
- •arrhythmias (clarification: Subjects with atrial fibrillation controlled for
- •>30 days prior to dosing are eligible); a history of acute coronary
- •syndromes (including myocardial infarction or unstable angina),
- •coronary angioplasty, or stenting within 6 months prior to
- •randomization; a history or evidence of current >=Class II cong
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