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

NCT01291433 | Completed Phase 3

• 1 other identifier: P081239
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 2

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 (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

Outcome Measures

Primary Outcomes (1)

• Sensory-motor neurological clinical assessment

  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

  18 months

Secondary Outcomes (14)

• Pain VAS

  6, 12, 18 months

• NPSI scale

  6, 12, 18 months

• Paresthesia VAS

  6, 12, 18 months

• Frequence of paresthesia

  6, 12, 18 months

• ODSS

  6, 12, 18 months

Study Arms (2)

PENTOCLO

EXPERIMENTAL

Association pentoxifylline, tocopherol and clodronate

Drug: Pentoxifylline; Drug: Tocopherol acetate; Drug: Clodronic Acid

Placebo

PLACEBO COMPARATOR

Triple placebo

Drug: Pentoxifylline placebo; Drug: Tocopherol placebo; Drug: Clodronate placebo

Interventions

Pentoxifylline placebo DRUG

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

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

Placebo

Pentoxifylline DRUG

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

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

PENTOCLO

Tocopherol acetate DRUG

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

Also known as: Tocopherol alpha-acetate

PENTOCLO

Clodronic Acid DRUG

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

Also known as: Clodronate disodium

PENTOCLO

Tocopherol placebo DRUG

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

Placebo

Clodronate placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Groupe Hospitalier Pitié-Salpêtrière

Paris, France

Location

Hôpital Saint-Louis

Paris, France

Location

Related Publications (1)

• Pradat PF, Maisonobe T, Psimaras D, Lenglet T, Porcher R, Lefaix JL, Delanian S. [Radiation-induced neuropathies: collateral damage of improved cancer prognosis]. Rev Neurol (Paris). 2012 Dec;168(12):939-50. doi: 10.1016/j.neurol.2011.11.013. Epub 2012 Jun 27. French.

  PMID: 22742890 DERIVED

MeSH Terms

Conditions

Radiation induced brachial plexopathy

Interventions

Pentoxifylline; alpha-Tocopherol; Clodronic Acid

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tocopherols; Vitamin E; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals

Study Officials

• Sylvie Delanian, MD, PhD

  Oncologie-Radiothérapie, Hôpital Saint Louis , Paris, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2011
• First Posted: February 8, 2011
• Study Start: March 1, 2011
• Primary Completion: May 1, 2017
• Study Completion: October 1, 2017
• Last Updated: December 8, 2017

Record last verified: 2017-12

Locations

FR (2)