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

NCT ID: NCT01291433

Last Updated: 2017-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2017-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Radiation Induced Brachial Plexopathy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

PENTOCLO

Association pentoxifylline, tocopherol and clodronate

Group Type EXPERIMENTAL

Pentoxifylline

Intervention Type DRUG

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

Tocopherol acetate

Intervention Type DRUG

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

Clodronic Acid

Intervention Type DRUG

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

Placebo

Triple placebo

Group Type PLACEBO_COMPARATOR

Pentoxifylline placebo

Intervention Type DRUG

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

Tocopherol placebo

Intervention Type DRUG

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

Clodronate placebo

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pentoxifylline placebo

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

Intervention Type DRUG

Pentoxifylline

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

Intervention Type DRUG

Tocopherol acetate

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

Intervention Type DRUG

Clodronic Acid

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

Intervention Type DRUG

Tocopherol placebo

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

Intervention Type DRUG

Clodronate placebo

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

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

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

74 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sylvie Delanian, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oncologie-Radiothérapie, Hôpital Saint Louis , Paris, France

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 22742890 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

P081239

Identifier Type: -

Identifier Source: org_study_id