NCT03898908已完成2 期
Phase II, Multicentre Clinical Trial to Evaluate the Activity of Encorafenib and Binimetinib Administered Before Local Treatment in Patients With BRAF Mutant Melanoma Metastatic to the Brain
Grupo Español Multidisciplinar de Melanoma21 个研究点 分布在 1 个国家目标入组 48 人开始时间: 2019年7月18日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 21
- 主要终点
- Intracranial Objective Response (iORR) by Modified RECIST 1.1 Before Local Radiotherapy Treatment in Full Dataset
研究概览
简要总结
Phase II clinical trial, with two cohorts of patients included in parallel, all with melanoma BRAF mutated and brain metastases without previous local treatment in the brain. Cohort 1 will include patients with asymptomatic brain metastases and cohort 2 will include patients with symptomatic brain metastasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 of approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to the performance of any trial activities.
- •Histologically confirmed diagnosis of unresectable metastatic cutaneous melanoma, or unknown primary melanoma with one or more brain metastasis with a diameter of 10 to 50 mm, measured by contrast enhanced MRI.
- •Presence of a BRAF V600E or V600K mutation, or both, in their tumour tissue.
- •Barthel Index of Activities of Daily Living >
- •Subjects aged ≥ 18 years.
- •ECOG 0-1 in asymptomatic patients (cohort 1), 0-2 in symptomatic patients (cohort 2).
- •Adequate haematological function (Haemoglobin ≥ 9 g/dL, may have been transfused; Platelet count ≥ 100 × 109/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.)
- •Adequate hepatic function defined by a total bilirubin level ≤ 2.0 × the upper limit of normality (ULN) and AST and ALT levels ≤ 2.5 × ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
- •Serum Creatinine ≤ 2.0 x ULN or estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
- •Evidence of at least one measurable lesion as detected by radiological or photographic methods according to guidelines based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.
- •Naïve untreated patients or patients who have progressed on or after prior first line immunotherapy for unresectable locally advanced or metastatic melanoma, but it must have ended at least 6 weeks prior to randomization; prior adjuvant therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy or chemotherapy), BRAF or MEK inhibitors can be used in the adjuvant setting, providing the relapse does not occur during the adjuvant treatment or within 12 months after the end of it, and providing the adjuvant treatment with targeted therapy did not cause in the patient any grade 3-4 toxicity not including medically serious and reversible/controlled toxicities (ex: GGT elevation, CPK elevation, vomiting).
- •Steroids or anticonvulsants are allowed if clinically needed and are not being administered in an increasing dose.
- •Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥60 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
- •Normal functioning of daily living activities.
- •Willingness and ability to attend scheduled visits, follow the treatment schedule and undergo clinical tests and other study procedures.
排除标准
- •Uveal or mucosal melanoma.
- •History of leptomeningeal metastases, with the exception that they are only seen in brain MRI and the patient has ECOG 0-1 and no neurological symptoms (except for cohort 2, where symptomatic patients will be allowed if ECOG is 0-2).
- •Another cancer in the last five years, except for in situ carcinoma of the cervix or squamous cell carcinoma of the skin adequately treated or limited basal cell skin cancer adequately controlled.
- •History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease (RDD).
- •Any previous systemic chemotherapy treatment, extensive brain radiotherapy, targeted therapy for locally advanced unresectable or metastatic melanoma; Immunotherapy treatment is allowed but must have ended at least 6 weeks prior to randomization.
- •History of Gilbert's syndrome.
- •Previous treatment with a BRAF or MEK inhibitor in metastatic setting. This treatment will be allowed in the adjuvant setting (see above). Previous treatments with immunotherapy will be allowed in both the metastatic and adjuvant setting.
- •Known positive serology for human immunodeficiency virus, or an active hepatitis B or hepatitis C infection, or both.
- •Impaired cardiovascular function or clinically significant cardiovascular diseases "Clinically significant (i.e., active) cardiovascular disease: cerebrovascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), a LVEF < 50% evaluated by MUGA or echocardiography, or serious cardiac arrhythmia requiring medication or a triplicate average baseline QTc interval > 500 ms."
- •Uncontrolled arterial hypertension despite medical treatment.
- •Moderate (Child Pugh Class B) or severe (Child Pugh Class C) hepatic impairment.
- •Impairment of gastrointestinal function.
- •Neuromuscular disorders associated with high concentrations of creatine kinase.
- •Pregnant or nursing (lactating) women.
- •Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study.
- •Known hypersensitivity to encorafenib, binimetinib or their components.
- •Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v 4.03; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable.
- •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ highly effective birth control from screening to 180 days after the last dose of study treatment.
- •Known alcohol or drug abuse.
- •Inability to swallow tablets or capsules.
- •Total lactase deficiency or glucose-galactose malabsorption.
研究组 & 干预措施
COMBO450
Experimental
Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets
In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death.
干预措施: encorafenib (Drug)
COMBO450
Experimental
Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets
In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death.
干预措施: binimetinib (Drug)
COMBO450
Experimental
Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets
In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death.
干预措施: Whole brain radiation therapy (Radiation)
COMBO450
Experimental
Encorafenib - Orally, 75 mg and 50 mg capsules Binimetinib - Orally, 15 mg tablets
In each cohort, patients will be treated with encorafenib 450 mg once daily and binimetinib 45 mg twice daily until PD or death.
干预措施: Radiosurgery/stereotactic radiosurgery (Radiation)
结局指标
主要结局
Intracranial Objective Response (iORR) by Modified RECIST 1.1 Before Local Radiotherapy Treatment in Full Dataset
时间窗: 24 months after start of treatment
iORR calculated as the proportion of patient with a best overall intracranial response of complete response (CR) or partial response (PR) before local treatment according to modified RECIST 1.1. Modified RECIST 1.1 consists of: Up to 5 intracranial lesions could be selected as target lesions Target lesions might have a longest diameter ≥ 5 mm when evaluated by contrast-enhanced MRI This endpoint was also independently reported in patients with symptomatic and asymptomatic brain metastasis.
次要结局
- Duration of Intracranial Response(Throughout the study period, up to approximately 24 months)
- Intracranial Progression-free Survival (iPFS) by RECIST 1.1(Throughout the study period, up to approximately 24 months)
- Extracranial Progression-free Survival (ePFS) in Both Cohorts(Throughout the study period, up to approximately 24 months)
- Intracranial Progression-free Rates(at 6 months (week 24), 12 months (week 48) and 24-month (week 96))
- Overall Survival(Throughout the study period, up to approximately 24 months)
- Overall Survival Rates(at 6 months, 12 month and 24-month)
- Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0(Throughout the study period, up to approximately 24 months)
- Change on Quality of Life at Week 8 in Both Cohorts Based on the EORTC QLQ 30 Scale(8 weeks)
- Change on Quality of Life at Week 24 in Both Cohorts Based on the EORTC QLQ 30 Scale(24 weeks)
- Extracranial Progression-free Rates(at 6 months (week 24), 12 months (week 48) and 24-month (week 96))
研究者
研究点 (21)
Loading locations...
相似试验
已完成
2 期
Dabrafenib and Trametinib for BRAF-inhibitor Pretreated PatientsMalignant MelanomaNCT02296996Universitair Ziekenhuis Brussel25
Unknown
2 期
Buparlisib in Melanoma Patients Suffering From Brain Metastases (BUMPER)Malignant MelanomaMetastasesNCT02452294University Hospital Tuebingen22
已完成
2 期
Trial to Evaluate the Efficacy and Safety of IVIEW-1201 in Acute Bacterial ConjunctivitisAcute Bacterial ConjunctivitisNCT05816070IVIEW Therapeutics Inc.129
已完成
2 期
LCCC 1128: Open Label Phase II Trial of the BRAF Inhibitor (Dabrafenib) and the MEK Inhibitor (Trametinib) in Unresectable Stage III and Stage IV BRAF Mutant Melanoma; Correlation of Resistance With the Kinome and Functional MutationsStage III MelanomaStage IV MelanomaUnresectable MelanomaBRAF Mutant MelanomaNCT01726738UNC Lineberger Comprehensive Cancer Center17
终止
2 期
Pembrolizumab in Treating Patients With Advanced Uveal MelanomaStage IIIA Uveal MelanomaStage IIIB Uveal MelanomaStage IIIC Uveal MelanomaStage IV Uveal MelanomaNCT02359851Vanderbilt-Ingram Cancer Center5