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Radiation Induced Brachial PlexopathyPhase 3PENTOCLONCT01291433

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

A Phase 3 study testing Pentoxifylline, Tocopherol acetate and Clodronic Acid in people with Radiation Induced Brachial Plexopathy, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 74 years
Conditions the study is for
Radiation Induced Brachial Plexopathy
What is being tested?
Pentoxifylline, Tocopherol acetate and Clodronic Acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
59 participants
Where
2 sitesFrance
Study dates
Mar 2011to Oct 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Groupe Hospitalier Pitié-Salpêtrière

    Paris

  • Hôpital Saint-Louis

    Paris

Other trials in France

About this study

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

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.

Read more

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.

Read the detailed 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.

Being tested
Pentoxifylline placebo, Pentoxifylline, Tocopherol acetate, Clodronic Acid, Tocopherol placebo
Medical subject headings
Radiation induced brachial plexopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pentoxifylline placeboDrug

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

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

  • PentoxifyllineDrug

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

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

  • Tocopherol acetateDrug

    Also called Tocopherol alpha-acetate

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

  • Clodronic AcidDrug

    Also called Clodronate disodium

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

  • Tocopherol placeboDrug

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

  • Clodronate placeboDrug

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

Study groups in NCT01291433
Study groupRoleWhat they receive
PENTOCLOExperimentalAssociation pentoxifylline, tocopherol and clodronate
Receives: Drug: Pentoxifylline; Drug: Tocopherol acetate; Drug: Clodronic Acid
PlaceboPlacebo comparatorTriple placebo
Receives: Drug: Pentoxifylline placebo; Drug: Tocopherol placebo; Drug: Clodronate placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 18 months

Secondary outcomes (14)

  1. Pain VAS

    Visual analog scale for pain

    Measured: 6, 12, 18 months

  2. NPSI scale

    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]

    Measured: 6, 12, 18 months

  3. Paresthesia VAS

    Visual analog scale for paresthesia

    Measured: 6, 12, 18 months

  4. Frequence of paresthesia

    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)

    Measured: 6, 12, 18 months

  5. ODSS

    Overall disability sum score: Checklist for upper limb (5 items) and lower limb (7 items)

    Measured: 6, 12, 18 months

  6. Muscle testing

    Semi-quantitative manual muscle strength assessment on a 0 to 5 scale, separately for each muscle.

    Measured: 6, 12, 18 months

  7. Neurological examination

    Evaluation of sensitivity, motricity and reflex

    Measured: 6, 12, 18 months

  8. Motor assessment of complex movements

    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

    Measured: 6, 12, 18 months

  9. Quality of life

    Global quality of life as evaluated by SF36 questionnaire

    Measured: 6, 12, 18 months

  10. Global clinical impression

    Patient global impression of change (PGIC) and clinical global impression of change (CGIC)

    Measured: 6, 12, 18 months

  11. Electromyography

    Electromyography of upper / lower limbs

    Measured: 6, 12, 18 months

  12. Clinical symptoms evaluation

    Clinical evaluation looking for upper digestive disorders (nausea, vomiting, epigastralgia), lower digestive disorders (diarrhea), vascular disorders (cephalalgia, vertigo, flush, deep asthenia), bleeding (hematoma)

    Measured: 6, 12, 18 months

  13. Biological evaluation

    evaluation of biological parameters: blood cell count, platelets, sedimentation velocity, C-reactive protein, prothrombin time, TCK, calcemia, protidemia, LDH, creatininemia, phosphokinase creatine (CPK)

    Measured: 6, 12, 18 months

  14. Cardiovascular evaluation

    As evaluated by:

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

    Measured: 6, 12, 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionMay 2017
  4. Study completionOct 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01291433
Sponsor's protocol ID
P081239
Acronym
PENTOCLO
Status last verified
Dec 2017
First submitted
2 Feb 2011
Last updated
8 Dec 2017
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 22742890

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pentoxifylline, Tocopherol acetate and Clodronic Acid in people with Radiation Induced Brachial Plexopathy, run by Assistance Publique - Hôpitaux de Paris at 2 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sensory-motor neurological clinical assessment (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01291433, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2017.

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