NCT05097378Unknown2 期
Perioperative Encorafinib+Binimetinib in BRAFV600 Mutant Clinically Detected AJCC Stage III (B/C/D) or Oligometastatic Stage IV Melanoma
CCTU- Cancer Theme1 个研究点 分布在 1 个国家目标入组 45 人开始时间: 2022年1月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Pathological response rate
研究概览
简要总结
A two-arm, randomised trial investigating the response of encorafenib and binimetinib compared to standard adjuvant therapy.
详细描述
A phase II, multi-centre, open label, randomised trial.
The trial will assess the delivery, response rate, treatment compliance, efficacy and safety of encorafenib and binimetinib compared to standard adjuvant therapy in patients with BRAFV600 mutant clinically detected AJCC stage III(B/C/D) or oligometastatic stage IV Melanoma.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent to participate
- •Aged ≥ 18 years old
- •AJCC 8th edition stage III (B/C/D), or extracranial oligometastatic stage IV BRAFV600 mutant melanoma, based on histological/cytological and radiological assessments for which surgery is planned, and resection is expected to remove all known tumour(s) with R0 resection margins. 'Oligometastatic stage IV' is defined for the purpose of this trial as M stage disease confined to a single body organ excluding the brain that can be readily removed surgically with anticipated clear margins
- •For stage III patients, confirmation of no evidence of distant metastatic disease using preferred imaging modalities including CT body or PET/CT and CT or MRI head
- •For stage IV patients, confirmation of no evidence of unresectable metastatic disease, or metastatic disease in more than 1 body organ, using preferred imaging modalities including CT body or PET/CT and CT or MRI head. The site of metastasis should not be in bone, or CNS, or in any other body site where complete resection is not feasible
- •The planned resectable disease must be radiologically measurable using standard imaging modalities.
- •Baseline tumour assessments must be done within 28 days prior to randomisation
- •BRAF V600E or V600K mutation confirmation
- •Received no prior BRAF or MEK inhibitors
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Predicted life expectancy >12 months
- •Normal QTc interval (<480msec) on ECG and left ventricular ejection fraction within normal limits, assessed by echocardiogram or MUGA
- •Adequate bone marrow function defined as:
- •Absolute neutrophil count (ANC) ≥1.5 x 109 /L
- •Haemoglobin (Hb) ≥ 90 g/L
- •Platelets ≥100 x 109 /L
- •Adequate liver function defined as:
- •Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤2.5 x upper limit of normal range (ULN)
- •Total bilirubin <1.5 x ULN (except if the patient has Gilbert Syndrome or liver metastases, in which case the bilirubin must be <3 x ULN)
- •Adequate renal function defined as:
- •a serum creatinine ≤1.5 x ULN or
- •calculated creatinine clearance by Cockcroft-Gault of ≥40 mL/min
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and PROM questionnaires and other procedures described in the protocol
- •Women of child-bearing potential (WCBP) and all sexually active male patients must agree to use effective contraception methods throughout treatment
- •Be able to swallow the trial medication
- •Confirmation of adequate diagnostic tumour tissue available for research studies
- •Exclusion criteria
- •Prior adjuvant therapy for resected primary or loco-regional melanoma
- •Other invasive malignancies diagnosed within the last 2 years which are not in complete remission, or for which additional therapy is required
- •Brain or bone metastases
- •Non-cutaneous primary site of melanoma
- •Prior radiotherapy to the site planned for surgery
- •History or current evidence of retinal vein occlusion (RVO) or risk factors for RVO (uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)
- •Left ventricular function <50%
- •Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:
- •Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months
- •Uncontrolled hypertension
- •Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV or frequent angina
- •Patients with baseline QTC interval > 480 msec on electrocardiogram (ECG)
- •Left ventricular ejection fraction below the lower limit of normal
- •Presence of active infection
- •Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C
- •Known allergy or hypersensitivity to Encorafenib or Binimetinib, or their excipients. Binimetinib contains lactose, so patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption will be excluded.
- •Women who are pregnant, plan to become pregnant or are lactating during the trial period
- •Use of any other investigational anti-cancer drugs (a washout period of 28 days would be required)
- •Use of strong inducers and inhibitors of CYP3A4 (Appendix 4 - Prohibited Medication)
- •Known HIV or active Hep B or Hep C infection
- •Patients who have neuromuscular disorders associated with elevated creatine phosphokinase (CK, e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
- •Autoimmune conditions requiring regular or intermittent use of any systemic steroid or immunosuppressive drugs, with the exception of steroid inhalers
- •Any immunotherapy in the last 3 months
- 另有 2 项未显示
排除标准
- 未提供
研究组 & 干预措施
Standard Arm
Active Comparator
Immediate surgery followed by Investigator's choice of standard adjuvant therapy to commence within 12 weeks of surgery and to continue for up to 52 weeks.
干预措施: Standard Adjuvant Treatment (Drug)
EncoBini Arm
Experimental
Oral encorafenib 450mg once daily and oral binimetinib 45mg twice daily for 8 weeks pre-operative and for up to 44 weeks post-operative.
干预措施: Encorafenib + Binimetinib (Drug)
结局指标
主要结局
Pathological response rate
时间窗: During scheduled surgery
% of patients with a complete response using Haemotoxylin and Eosin staining of tumour removed at surgery.
次要结局
- Radiological response(Through study completion for an average of 12 months)
- Quality of life(Through study completion for an average of 12 months)
- Recruitment rate(Through study completion for an average of 12 months)
- Treatment compliance(Through study completion for an average of 12 months)
- Lymphoedema toxicity(Through study completion for an average of 12 months)
- Survival rate(Through study completion for an average of 12 months)
- Toxicity of treatment(Through study completion for an average of 12 months)
研究者
CCTU- Cancer Theme
Chief Investigator
Cambridge University Hospitals NHS Foundation Trust
研究点 (1)
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