Randomized Clinical Trial Evaluating Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy: the PENTOCLO Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 2
- 主要终点
- Sensory-motor neurological clinical assessment
研究概览
简要总结
Radiation-induced brachial plexopathy (RIP) is a rare and severe delayed peripheral nerve complication of radiotherapy, that is spontaneously irreversible with no medical treatment to limit or reduce symptoms. The investigators planed in RIP a randomized double blind clinical trial, using a pentoxifylline (P)- tocopherol (E)- clodronate combination versus placebo, to assess a possible symptomatic regression by a sensory-motor neurological quantifiable and reproducible score (modified Subjective Objective Medical management Analytic, SOMA).
The investigators previously developed a successful PE treatment in symptomatic RI injuries via the antioxidant pathway, in clinical phase II and III trails and experiments obtaining a major significant radiation-induced fibrosis regression, then the PE clodronate combination (PENTOCLO), obtaining a rapid and significant healing of mandible osteoradionecrosis and significant neurological signs regression (- 35% modified SOMA score at 18 months) in 50 partial RIP.
The aim of this phase III randomized clinical trial is to show PENTOCLO efficiency and its tolerance in long survival patients irradiated before for cancer and presenting with partial RIP of upper or lower legs.
The investigators calculated to include 60 patients to show a significant clinical difference between the two groups after 18 months of treatment: PENTOCLO[Pentoxifylline 400 (2x/d) + vitamine E 500 (2x/d) + intermittent Clodronate 800 (2/d, 5d/7)] versus triple placebo, with prednisone 20 (2d/7) for all patients.
RIP is assessed before treatment and every 6 months by a standardized sensory-motor neurological (SOMA 95 modified by NCI-CTC 99) score used for main criteria at M18, and various neurological scales of assessment (Visual Analog Scale for pain / VAS for paresthesia, Neuropathic Pain Symptom Inventory [NPSI], Overall Disability Sum Score [ODSS], muscle testing, Nine hole peg test / Timed 25-Foot Walk), quality of life (SF36, Patient Global Impression of Change and Clinical Global impression of Change [PGIC/ CGIC]) and electrophysiology.
详细描述
The aim of this phase III randomized clinical trial is to show PENTOCLO efficiency and its tolerance in long survival patients irradiated before for cancer and presenting with partial RIP of upper or lower legs.
We calculated to include 60 patients to show a significant clinical difference between the two groups after 18 months of treatment: PENTOCLO [Pentoxifylline 400 (2x/d) + vitamine E 500 (2x/d) + intermittent Clodronate 800 (2/d, 5d/7)] versus triple placebo, with prednisone 20 (2d/7) for all patients.
RIP is assessed before treatment and every 6 months by a standardized sensory-motor neurological (SOMA 95 modified by NCI-CTC 99) score used for main criteria at M18, and various neurological scales of assessment (Visual Analog Scale [VAS] for pain / VAS for paresthesia, Neuropathic Pain Symptom Inventory [NPSI], Overall Disability Sum Score [ODSS], muscle testing, Nine hole peg test / Timed 25-Foot Walk), quality of life (SF36, Patient Global Impression of Change and Clinical Global impression of Change [PGIC/ CGIC]) and electrophysiology.
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
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Past-history of post-operative or exclusive irradiation (RT) for currently in remission cancer, in particular
- •breast cancer with breast or thoracic anterior wall RT; axilla-subclavicular lymph nodes RT; sometimes lung or head/neck cancer
- •Lymphoma (Hodgkin or non Hodgkin) with axilla-subclavicular RT (upper limb) or lumbar-aortic (lower limbs) or testis tumor
- •Delay RT-RIP more than 6 months, but partial RIP
- •Neurological injury in irradiated volume confirmed by EMG
- •Patient living within distance compatible with day-hospitalization
- •Use of effective contraception for fertile women
- •Signed written informed consent (in case of motor paralysis informed consent is signed by a witness)
排除标准
- •Localized or metastatic cancer recurrence (axillar MRI or PET scan)
- •Complete plexus injury with total motor paralysis of upper/ lower limb for more than 2 years
- •Associated neurological disease that may interferer with the assessment of endpoints
- •Hemorrhage, disease with hemorrhagic risk, unbalanced diabetes
- •Known hypersensitivity to Pentoxifylline, one of the excipients or biphosphonates
- •Renal failure, liver failure or decompensated heart failure
- •Taking another biphosphonate
- •Evolving virosis (hepatitis, herpes, zona) or live vaccine (influenza)
- •Uncontrolled psychotic condition
- •Informed consent not obtained
- •Fertile women who do not want or cannot use effective contraception during the administration of study drugs
- •Women pregnant or nursing
研究组 & 干预措施
Placebo
Triple placebo
干预措施: Tocopherol placebo (Drug)
PENTOCLO
Association pentoxifylline, tocopherol and clodronate
干预措施: Pentoxifylline (Drug)
PENTOCLO
Association pentoxifylline, tocopherol and clodronate
干预措施: Tocopherol acetate (Drug)
PENTOCLO
Association pentoxifylline, tocopherol and clodronate
干预措施: Clodronic Acid (Drug)
Placebo
Triple placebo
干预措施: Pentoxifylline placebo (Drug)
Placebo
Triple placebo
干预措施: Clodronate placebo (Drug)
结局指标
主要结局
Sensory-motor neurological clinical assessment
时间窗: 18 months
Sensory-motor neurological clinical assessment of RIP patients as measured with SOMA scale (Subjective Objective Medical management Analytic involving tools) modified by NCI-CTC99 scale
次要结局
- Muscle testing(6, 12, 18 months)
- Cardiovascular evaluation(6, 12, 18 months)
- NPSI scale(6, 12, 18 months)
- Electromyography(6, 12, 18 months)
- ODSS(6, 12, 18 months)
- Motor assessment of complex movements(6, 12, 18 months)
- Paresthesia VAS(6, 12, 18 months)
- Frequence of paresthesia(6, 12, 18 months)
- Pain VAS(6, 12, 18 months)
- Neurological examination(6, 12, 18 months)
- Quality of life(6, 12, 18 months)
- Global clinical impression(6, 12, 18 months)
- Clinical symptoms evaluation(6, 12, 18 months)
- Biological evaluation(6, 12, 18 months)