Reversing External-beam Radiotherapy-associated Fibrosis Syndrome: an Interventional Bayesian Adaptive Randomized-controlled Orphan Drug Platform Trial for Orodental Sequelae (Reverse-fibrose)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Safety and adverse events
研究概览
简要总结
To find out if adding medication can help treat or prevent lymphedema and/or fibrosis related to radiation therapy, in survivors of head and neck cancer. Researchers will compare these drugs to find the most effective therapy for preventing or limiting these side effects.
详细描述
Primary Objectives
-
Determine the relative utility of candidate agents to reduce clinician-rated radiation lymphedema/fibrosis
-
Hyp 1: Participants receiving candidate agent(s) will exhibit a proportional lower rate of Common Toxicity Criteria- Adverse Event (CTC-AE v5.0) rating of Grade 2 or greater on either "Fibrosis deep connective tissue" or "Superficial soft tissue fibrosis" by formal clinician assessment at 12 months post-randomization.
-
Hyp 2: Participants receiving candidate agent(s) will exhibit a proportional lower rate of objective lymphedema/fibrosis rated as "moderate/severe" grade at any head and neck subsite as measured by the Head and Neck External Lymphedema and Fibrosis (HN-ELAF) Assessment Criteria by a certified lymphedema specialist at 12 months post-randomization.
-
Determine the relative effect size observed of candidate agent(s) to reduce objective imaging-derived measures of radiation lymphedema/fibrosis-related sequalae [Primary]
-
Hyp 3: Participants receiving candidate agent(s) will exhibit a proportionally lower rate of objective DIGEST-detected swallowing dysfunction 12 months post-randomization.
-
Hyp 4: Participants receiving candidate agent(s) will exhibit a proportional lower rate of objective MRI-detected difference between 6- and 18-month post-randomization quantitative T1 (T1 mapping) intensity for paired muscle swallowing/neck/masticator muscles receiving >=40Gy post-randomization.
Secondary Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Eligibility Criteria Eligibility criteria (observational registry or randomization)
- •Prior history of head and neck cancer with no active disease.
- •Treated previously with radiotherapy with prescribed dose (greater or equal to 30Gy) to unilateral or bilateral neck(s)
- •Detectable CTC-AE G2+ lymphedema/fibrosis at >6 months post-radiotherapy.
- •No active liver disease (Child-Pugh class B-C), cirrhosis, nor active alcoholism, nor history of ulcers.
- •No history of myopathy/rhabdomyolysis.
- •Creatinine clearance <30mL/min.
- •No history of acute myocardial infarction or severe coronary disease.
- •Non-pregnant/post-menopausal, or male.
- •No history of diabetes mellitus
- •Allergy/hypersensitivity to HMG Co-A reductase inhibitor and/or xanthine derivatives, e.g., caffeine, theophylline, theobromine
- •No contraindications for magnetic resonance imaging a Subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional
排除标准
- •Active liver disease (Child-Pugh class B-C), cirrhosis, nor active alcoholism.
- •History of myopathy/rhabdomyolysis.
- •History of acute myocardial infarction or severe coronary disease.
- •Pregnant/post-menopausal, or male.
- •History of diabetes mellitus.
- •Allergy/hypersensitivity to Hydroxymethylglutaryl-coenzyme A (HMG Co-A) reductase inhibitor and/or xanthine derivatives, e.g., caffeine, theophylline, theobromine.
- •Contraindications for MRI Subject to the discretion of the treating physician and Principal Investigator (PI), as the MRI may be optional
- •Participants who are receiving any other investigational agents.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to statins, hemorheologic agents or other agents used in study
- •Participants with psychiatric illness/social situations that would limit compliance with study requirements.
研究组 & 干预措施
Treatment with SoC (Control)
No pharmacologic intervention (control)
干预措施: Standard of Care (SOC) (Other)
Treatment with Ketoprofen TID
75 mg for 12 months
干预措施: ketoprofen (Drug)
Treatment with Pirfenidone TID
801 mg for 12 months
干预措施: Pirfenidoneone (Drug)
Treatment with Pentoxifylline TID + Tocopherol
400 mg/1000 IU vitamin E for 12 months
干预措施: Pentoxifylline (Drug)
Treatment with Pravastatin QD
40 mg/day for 12 months
干预措施: Pravastatin (drug) (Drug)
Treatment with Pentoxifylline TID + Tocopherol
400 mg/1000 IU vitamin E for 12 months
干预措施: tocopherol (Drug)
结局指标
主要结局
Safety and adverse events
时间窗: Through study completion; an average of 1 year
Incidence of Adverse of Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events
次要结局
未报告次要终点