Radiation Induced Brachial Plexopathy | Trial of Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy
Radiation Induced Brachial Plexopathy research study
What is the primary objective of this study?
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.
Who is eligible to participate?
Inclusion Criteria: - 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) Exclusion Criteria: - 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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Radiation Induced Brachial Plexopathy
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Pentoxifylline placeboPlacebo for pentoxifylline 400 mg, 1 cp twice a day (7d/7)
Drug:PentoxifyllinePentoxifylline 400 mg: 1 cp twice a day (7d/7)
Drug:Tocopherol acetateTocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7)
Drug:Clodronic AcidClodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)
Drug:Tocopherol placeboPlacebo for Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7)
Drug:Clodronate placeboPlacebo for clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
PENTOCLOAssociation pentoxifylline, tocopherol and clodronate
Start Date: March 2011
Completed Date: October 2017
Phase: Phase 3
Primary Outcome: Sensory-motor neurological clinical assessment
Secondary Outcome: Pain VAS
Study sponsors, principal investigator, and references
Principal Investigator: Sylvie Delanian, MD, PhD
Lead Sponsor: Assistance Publique - Hôpitaux de Paris