Trial of Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy
Condition: Radiation Induced Brachial Plexopathy
MeSH terms: Brachial Plexus Neuropathies; Radiation Injuries
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Pentoxifylline placebo; Pentoxifylline; Tocopherol acetate; Clodronic Acid; Tocopherol placebo; Clodronate placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Placebo for pentoxifylline 400 mg, 1 cp twice a day (7d/7); Pentoxifylline 400 mg: 1 cp twice a day (7d/7); Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7); Clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday); Placebo for Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7); Placebo for clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)
Other intervention name(s): Placebo for pentoxifylline 400 mg, 1 cp twice a day (7d/7); Pentoxifylline 400 mg: 1 cp twice a day (7d/7); Tocopherol alpha-acetate; Clodronate disodium
Intervention MeSH terms: Clodronic Acid; Tocopherols; Vitamin E; Tocotrienols; alpha-Tocopherol; Pentoxifylline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment