Clinical Trial: Trial of Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized Clinical Trial Evaluating Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy: the PENTOCLO Trial

Brief 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

Detailed Summary:

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.


Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Sensory-motor neurological clinical assessment [ Time Frame: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pain VAS [ Time Frame: 6, 12, 18 months ]
    Visual analog scale for pain
  • NPSI scale [ Time Frame: 6, 12, 18 months ]
    NPSI (Neuropathic Pain Symptom Inventory) pain scale to assess neuropathic pain by a self-questionnaire [Reference: Bouhassira et al. Development and validation of the neuropathic pain symptom inventory. Pain 2004;108(3):248-57]
  • Paresthesia VAS [ Time Frame: 6, 12, 18 months ]
    Visual analog scale for paresthesia
  • Frequence of paresthesia [ Time Frame: 6, 12, 18 months ]

    Evaluated on a 4-item scale:

    • Never
    • Occasional (several times each week or month)
    • Intermittent (several times a day)
    • Permanent (all day long and night)
  • ODSS [ Time Frame: 6, 12, 18 months ]
    Overall disability sum score: Checklist for upper limb (5 items) and lower limb (7 items)
  • Muscle testing [ Time Frame: 6, 12, 18 months ]
    Semi-quantitative manual muscle strength assessment on a 0 to 5 scale, separately for each muscle.
  • Neurological examination [ Time Frame: 6, 12, 18 months ]
    Evaluation of sensitivity, motricity and reflex
  • Motor assessment of complex movements [ Time Frame: 6, 12, 18 months ]

    Evaluated by two separate tests according to upper vs lower limb involvement:

    • Nine Hole Peg test for brachial injury
    • Timed 25-Foot Walk for lower limb symptoms
  • Quality of life [ Time Frame: 6, 12, 18 months ]
    Global quality of life as evaluated by SF36 questionnaire
  • Global clinical impression [ Time Frame: 6, 12, 18 months ]
    Patient global impression of change (PGIC) and clinical global impression of change (CGIC)
  • Electromyography [ Time Frame: 6, 12, 18 months ]
    Electromyography of upper / lower limbs
  • Clinical symptoms evaluation [ Time Frame: 6, 12, 18 months ]
    Clinical evaluation looking for upper digestive disorders (nausea, vomiting, epigastralgia), lower digestive disorders (diarrhea), vascular disorders (cephalalgia, vertigo, flush, deep asthenia), bleeding (hematoma)
  • Biological evaluation [ Time Frame: 6, 12, 18 months ]
    evaluation of biological parameters: blood cell count, platelets, sedimentation velocity, C-reactive protein, prothrombin time, TCK, calcemia, protidemia, LDH, creatininemia, phosphokinase creatine (CPK)
  • Cardiovascular evaluation [ Time Frame: 6, 12, 18 months ]

    As evaluated by:

    • Heart rate
    • Blood pressure lying and standing after 5 minutes orthostatism
    • Electrocardiogramm


Original Secondary Outcome:

  • Pain VAS [ Time Frame: 6, 12, 18 months ]
    Visual analog scale for pain
  • NPSI scale [ Time Frame: 6, 12, 18 months ]
    NPSI (Neuropathic Pain Symptom Inventory) pain scale to assess neuropathic pain by a self-questionnaire [Reference: Bouhassira et al. Development and validation of the neuropathic pain symptom inventory. Pain 2004;108(3):248-57]
  • Paresthesia VAS [ Time Frame: 6, 12, 18 months ]
    Visual analog scale for paresthesia
  • Frequence of paresthesia [ Time Frame: 6, 12, 18 months ]

    Evaluated on a 4-item scale:

    • Never
    • Occasional (several times each week or month)
    • Intermittent (several times a day)
    • Permanent (all day long and night)
  • ODSS [ Time Frame: 6, 12, 18 months ]
    Overall disability sum score: Checklist for upper limb (5 items) and lower limb (7 items)
  • Muscle testing [ Time Frame: 6, 12, 18 months ]
    Semi-quantitative manual muscle strength assessment on a 0 to 5 scale, separately for each muscle.
  • Neurological examination [ Time Frame: 6, 12, 18 months ]
    Evaluation of sensitivity, motricity and reflex
  • Motor assessment of complex movements [ Time Frame: 6, 12, 18 months ]

    Evaluated by two separate tests according to upper vs lower limb involvement:

    • Nine Hole Peg test for brachial injury
    • Timed 25-Foot Walk for lower limb symptoms
  • Quality of life [ Time Frame: 6, 12, 18 months ]
    Global quality of life as evaluated by SF36 questionnaire
  • Global clinical impression [ Time Frame: 6, 12, 18 months ]
    Patient global impression of change (PGIC) and clinical global impression of change (CGIC)
  • Electromyography [ Time Frame: 6, 12, 18 months ]
    Electromyography of upper / lower limbs
  • Clinical symptoms evaluation [ Time Frame: 6, 12, 18 months ]
    Clinical evaluation looking for upper digestive disorders (nausea, vomiting, epigastralgia), lower digestive disorders (diarrhea), vascular disorders (cephalalgia, vertigo, flush, deep asthenia), bleeding (hematoma)
  • Biological evaluation [ Time Frame: 6, 12, 18 months ]
    evaluation of biological parameters: blood cell count, platelets, sedimentation velocity, C-reactive protein, prothrombin time, TCK, calcemia, protidemia, LDH, creatininemia, phosphokinase creatine (CPK)
  • Cardiovascular evaluation [ Time Frame: 6, 12, 18 months ]

    As evaluated by:

    • Heart rate
    • Blood pressure lying and standing after 5 minutes orthostatism
    • Electrogardiogramm


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: February 2, 2011
Date Started: March 2011
Date Completion: October 2016
Last Updated: June 8, 2016
Last Verified: June 2016