The Efficacy of Cabozantinib in Advanced SAlivary Gland Cancer Patients, a Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- overall response rate
研究概览
简要总结
Phase 2 clinical trial on the efficacy of cabozantinib in locally advanced, recurrent and/or metastatic salivary gland cancer patients.
详细描述
Rationale: Salivary gland cancer (SGC) is a rare cancer with 24 histological subtypes. Treatment options for locally advanced and/or metastatic SGC are limited. The tyrosine kinase inhibitor cabozantinib suppresses tumor growth, angiogenesis, and metastasis, and has been approved for renal cell carcinoma and thyroid cancer. Cabozantinib may also be of value in advanced SGC because c-MET, one of the targets of cabozantinib, is frequently overexpressed in SGC.
Objectives: To assess the objective response rate (ORR), progression free survival (PFS), overall survival (OS), duration of response (DoR), toxicity, and quality of life (QoL) of patients with advanced SGC treated with cabozantinib in 3 cohorts: salivary duct carcinoma (SDC), adenoid cystic carcinoma (ACC), other SGC's.
Study design: Single arm, single center, phase II clinical trial in 3 cohorts: ACC, SDC and other SGC's.
Study population: Patient with c-MET positive, locally advanced, recurrent, and/or metastatic SGC.
Intervention: Cabozantinib tablets 60 mg once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw for a maximum duration of 2 years.
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
- •Disease specific
- •locally advanced, recurrent, and/or metastatic SGC (excluding sarcomas and mesenchymal tumors)
- •c-MET positive disease
- •Measurable disease per RECIST version 1.1 Cohort-specific criteria
- •SDC cohort: direct inclusion (no objective tumor growth prior to inclusion needed)
- •ACC cohort: inclusion after objective growth in the last three months or complaints due to the disease
- •Other SGC's: inclusion after objective growth in the last three months or complaints due to the disease General conditions
- •Age ≥18 years
- •Eastern Cooperative Oncology Group performance status of 0 or
- •Normal number of neutrophils and thrombocytes
- •Liver function: ALT and AST < 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN (except for Gilbert's syndrome), serum albumin ≥28 g/L
- •Renal function: creatinine < 1.5 x ULN or calculated creatinine clearance ≥ 40 ml/min, Urine protein/creatinine ratio ≤113.1 mg/mmol (≤1 mg/mg) or 24-hour urine protein <1 g
- •Hemoglobin A1c (HbA1c) ≤ 8% or a fasting serum glucose ≤ 9 mmol/l
排除标准
- •General conditions
- •A known allergy for cabozantinib or its components
- •Long QT-syndrome
- •Pregnancy or lactation
- •Patients (M/F) with reproductive potential not implementing adequate contraceptives measures
- •Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before inclusion
- •Major surgery within 3 months before randomization. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery at least 10 days before inclusion
- •Uncontrolled illness including, but not limited to cardiovascular disorders including symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias, uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg, or diastolic BP > 100 mm Hg, stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before inclusion, serious active infections Concomitant treatments
- •Concomitant (or within 4 weeks before inclusion) administration of any other experimental drug under investigation.
- •Concurrent treatment with any other anti-cancer therapy.
- •Concomitant anticoagulation. Low dose aspirin for cardioprotection and low dose LMWH are permitted.
- •Radiation therapy within the last 4 weeks before inclusion
研究组 & 干预措施
cabozantinib
cabozantinib 60 mg tablets OD
干预措施: Cabozantinib (Drug)
结局指标
主要结局
overall response rate
时间窗: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the response rate until progressive disease
Response will be measured according to RECIST version 1.1, the overall response rate is defined as the sum of the complete remissions plus partial responses. The best response will be used in each patient
次要结局
- progression free survival(every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses PFS until progressive disease)
- overall survival(Every OPD visit (starting with every 2 weeks, increasing to every 12 weeks after 1 year))
- duration of response(every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses duration of response until progressive disease)
- clinical benefit rate(every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the clinical benefit rate until progressive disease)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(through study completion. At every visit AE's will be recorded. Scheduled visits will be planned 2, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92 and 104 weeks after start of treatment)
- quality of life based on the EORTC QLQ-C30 questionnaire(patients are asked to fill in the questionnaires in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication).)
- quality of life based on the EORTC QLQ-H&N35 questionnaire(patients are asked to fill in the questionnaires in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication).)
- quality of life based on the PSSHN questionnaire(patients are asked to fill in the questionnaire in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication)..)
- pain level assessed by the VAS(visual analog scale) questionnaire(patients are asked to fill in the questionnaire in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication).)
- response rate with continues tumor shrinkage end-points(every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the response rate until progressive disease)
- circulating tumor DNA levels(circulating tumor DNA levels will be measured at baseline, at week 2, week 4 and before every evaluation CT/MRI scan.)
- correlation of c-MET immunohistochemical score with treatment response(c-MET will be measured once (before treatment). Response will be measured every 8 weeks (first year) and every 12 weeks (second year of treatment))