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

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.

Conditions

• Radiation Induced Brachial Plexopathy

Interventions

DRUG

Pentoxifylline placebo

Placebo for pentoxifylline 400 mg, 1 cp twice a day (7d/7)

DRUG

Pentoxifylline

Pentoxifylline 400 mg: 1 cp twice a day (7d/7)

DRUG

Tocopherol acetate

Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7)

DRUG

Clodronic Acid

Clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)

DRUG

Tocopherol placebo

Placebo for Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7)

DRUG

Clodronate placebo

Placebo for clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Sylvie Delanian, MD, PhD · Oncologie-Radiothérapie, Hôpital Saint Louis , Paris, France

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

74 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-03-31

Primary Completion

2017-05-31

Completion

2017-10-31

Countries

• France

Study Locations