NCT01256359已完成2 期
A Double Blind Randomised Phase 2 Trial of Docetaxel With or Without AZD6244 in wt BRAF Advanced Melanoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 83
- 试验地点
- 1
- 主要终点
- Progression Free Survival
研究概览
简要总结
This is a randomised, double-blind placebo controlled phase 2 trial. Patient will be randomly assigned 1:1 between 2 treatment arms. They will receive either docetaxel 75mg/m2 IV and placebo given bd, or AZD6244 75mg bd daily with docetaxel 75mg/m2 IV. Docetaxel will be administered every 3 weeks for a maximum 6 cycles, but AZD6244/placebo may be continued beyond this, until disease progression. The objective is to assess whether the combination of AZD6244 with docetaxel is worthy of evaluation in a definitive randomised study, with the null hypothesis being that the combination has activity similar to that of docetaxel alone in this population. After consent has been obtained mutational analysis of tumour BRAF will be performed on archival tumour tissue, where this information is not already known, to assess eligibility for the study. If there is no archival tissue a fresh biopsy will be requested from the patient. A blood sample will also be taken for future genetic analysis. Once taking part in the trial patients will need to attend their oncology unit regularly for monitoring and the delivery of treatment. Patients will undergo complete physical examination at screening, on C1D1, C1D8, C1D15, C2D1, C2D8 and day 1 of every subsequent cycle. Blood for haematology, biochemistry and clotting will be taken at each of these visits. A 12 lead ECG will be performed at screening . Disease assessment will be by CT scanning using modified RECIST criteria after 9 and 18 weeks, then every 3 months until disease progression.
详细描述
No further information in addition to what has been provided in the brief summary
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
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged >/= 16 years
- •Able to provide evidence from an accredited laboratory of wt BRAF status for their melanoma, or ascertainment of wt BRAF status from a sample of melanoma provided for mutational analysis in Oxford.
- •Unresectable stage 3 or 4, histologically proven cutaneous or unknown primary melanoma
- •At least 1 lesion, not previously irradiated, that can be accurately measured on CT or MRI as defined by modified RECIST criteria
- •ECOG performance score of 0 or
- •Life expectancy of at least 12 weeks.
- •The patient is willing to give consent to the main study and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.
- •Haematological and biochemical indices within the ranges shown below. Lab Test Value required Haemoglobin (Hb) >10g/dL White Blood Count (WBC) > 3x109/L Platelet count > 100,000/μL Absolute Neutrophil count > 1.5x109/L; Serum bilirubin ≤ 1.2 x ULN AST (SGOT) or ALT ≤ 2.5 x ULN LDH ≤ 2 x ULN Creatinine clearance (Cockcroft-Gault) >50 ml/min
排除标准
- •Any anti-cancer therapy (including radiotherapy and participation in other clinical trials) within 28 days prior to Day
- •Prior DNA damaging agents or cytotoxic chemotherapy for metastatic melanoma.
- •Any unresolved toxicity from prior anti-cancer therapy that is greater than CTCAE grade
- •Pregnancy or breastfeeding women. Female patients must have a negative urinary or serum pregnancy test or have evidence of post-menopausal status (defined as absence of menstruation for > 12 months, bilateral oophrectomy or hysterectomy).
- •Grade ≥2 peripheral neuropathy at study entry.
- •Patients of reproductive potential who are not willing to use adequate contraceptive measures for the duration of the study (both male and female patients)
- •Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80
- •Ocular or mucosal malignant melanoma
- •Another active malignancy within the past five years.
- •Evidence of brain metastases, unless surgically resected/stereotactic radiosurgery treated brain metastasis with no evidence of relapse on cerebral MRI, or treated brain metastasis and stable off treatment, including steroids, for 3 months.
- •Clinically significant and uncontrolled major medical condition(s): such as active infection, bleeding diathesis.
- •Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV.
- •Cardiac conditions, including uncontrolled hypertension (BP>160/100 despite treatment), heart failure NYHA class 2 or above, prior or current cardiomyopathy, myocardial infarction within 6 months or angina requiring nitrate therapy more than once a week.
- •Previous treatment with EGFR, ras, raf or MEK inhibitors.
- •Inability to swallow capsules, refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease) or significant bowel resection that would preclude adequate absorption.
- •Taking medication that significantly induces or inhibits CYP3A4.
研究组 & 干预措施
Docetaxel and AZD6244
Experimental
Docetaxel with AZD6244
干预措施: Docetaxel and AZD6244 (Drug)
Docetaxel and Placebo
Experimental
Docetaxel without AZD6244
干预措施: Docetaxel and placebo (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.
This is defined as time from date of randomisation to the first of date of progression (using CT scan, x-ray, MRI scan and clinical examination) using modified RECIST (v1.1) criteria or date of death (events). For patients without an event, the time from date of randomisation to date last known alive will be the censored PFS time.
次要结局
- Biochemistry - Phosphate(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Sodium(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Objective Response Rate(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.)
- Biochemistry - LDH(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Physical Exam - Skin(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Physical Exam - Abdomen(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Physical Exam - Extremities(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Physical Exam - Neurological(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Physical Exam - Other(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Overall Survival(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.)
- Overall Survival Results - Post Final Analysis(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.)
- Vital Signs - Temperature(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Vital Signs - Pulse Rate(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Vital Signs - Systolic Blood Pressure(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Vital Signs - Diastolic Blood Pressure(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Haematology - Haemoglobin(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Weight(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Physical Exam - Cardiovascular(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Physical Exam - Musculoskeletal(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Progression Free Survival Rate at 6 Months(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months.)
- Haematology - White Cell Count(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are median values across all time-points for all patients in that arm.)
- Haematology - Neutrophils(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Haematology - Platelets(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Calcium(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Potassium(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - ALT(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - AST(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Albumin(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Physical Exam - Head and Neck(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- ECG - Post-dose(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Urinalysis(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Biochemistry - GGT(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Physical Exam - Chest(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Physical Exam - Lymph Nodes(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- ECG - Pre-dose(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
- Biochemistry - Urea(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Bilirubin(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Alkaline Phosphatase(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Total Protein(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Biochemistry - Creatinine(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported value for each arm is median value across all time-points for all patients in that arm.)
- Physical Assessment - General Appearance(From randomisation date to date of PFS event, if they did not have an event by the end of trial datalock (01Oct2012), an average of 9.3 months. Reported values for each arm are total counts across all time-points for all patients in that arm.)
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