Overview

This trial is active, not recruiting.

Condition radiation induced brachial plexopathy
Treatments pentoxifylline placebo, pentoxifylline, tocopherol acetate, clodronic acid, tocopherol placebo, clodronate placebo
Phase phase 3
Sponsor Assistance Publique - Hôpitaux de Paris
Start date March 2011
End date May 2015
Trial size 59 participants
Trial identifier NCT01291433, P081239

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Association pentoxifylline, tocopherol and clodronate
pentoxifylline Pentoxifylline 400 mg: 1 cp twice a day (7d/7)
Pentoxifylline 400 mg: 1 cp twice a day (7d/7)
tocopherol acetate Tocopherol alpha-acetate
Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7)
clodronic acid Clodronate disodium
Clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)
(Placebo Comparator)
Triple placebo
pentoxifylline placebo Placebo for pentoxifylline 400 mg, 1 cp twice a day (7d/7)
Placebo for pentoxifylline 400 mg, 1 cp twice a day (7d/7)
tocopherol placebo
Placebo for Tocopherol alpha-acetate, 500 mg: 1 capsule twice a day (7d/7)
clodronate placebo
Placebo for clodronate disodium (clodronic acid) 800 mg: 2 cp per day, 5d/7 (from monday to friday)

Primary Outcomes

Measure
Sensory-motor neurological clinical assessment
time frame: 18 months

Secondary Outcomes

Measure
Pain VAS
time frame: 6, 12, 18 months
NPSI scale
time frame: 6, 12, 18 months
Paresthesia VAS
time frame: 6, 12, 18 months
Frequence of paresthesia
time frame: 6, 12, 18 months
ODSS
time frame: 6, 12, 18 months
Muscle testing
time frame: 6, 12, 18 months
Neurological examination
time frame: 6, 12, 18 months
Motor assessment of complex movements
time frame: 6, 12, 18 months
Quality of life
time frame: 6, 12, 18 months
Global clinical impression
time frame: 6, 12, 18 months
Electromyography
time frame: 6, 12, 18 months
Clinical symptoms evaluation
time frame: 6, 12, 18 months
Biological evaluation
time frame: 6, 12, 18 months
Cardiovascular evaluation
time frame: 6, 12, 18 months

Eligibility Criteria

Male or female participants from 18 years up to 74 years old.

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

Additional Information

Official title Randomized Clinical Trial Evaluating Combined Pentoxifylline-tocopherol-clodronate vs Placebo in Radiation-induced Brachial Plexopathy: the PENTOCLO Trial
Principal investigator Sylvie Delanian, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.