Evaluate The Efficacy and Safety Of Pregabalin In Prevention, Reduction of Oxaliplatin-Induced Painful Neuropathy (PreOx)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Daniel Ciampi Araujo de Andrade, University of Sao Paulo
ClinicalTrials.gov Identifier:
NCT01450163
First received: April 26, 2010
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

Oxaliplatin (Ox) is part of most treatment regimens for colorectal cancer. However, it may induce side effects, such as a specific injury to peripheral nerves called neuropathy. Ox-induced neuropathy is frequently painful. The presence of pain after its administration may hamper the full chemotherapeutic treatment of patients with colorectal cancer receiving this agent. Recently, it has been suggested that the appearance of acute neuropathy after oxaliplatin (Ox) infusion could predict the distal polyneuropathy seen some months after treatment. These two adverse events related to Ox treatment probably share different mechanistic backgrounds. However, recent experimental data suggest that both types of peripheral neuropathies are able to induce central sensitization, a major step to the occurrence of chronic pain. Pregabalin is a molecule used to teat neuropathic pain since it can diminish the peripheral sensitization seen in this painful condition. Recently, it has also been shown that pregabalin can be used to treat neuropathic pain related to Ox treatment. In the present study, we will test the hypothesis that Pregabalin administrated exclusively for three days before and three days after the Ox infusion is able to prevent the occurrence of pain secondary to both the acute and chronic Ox-associated neuropathies. In the classical FLOX chemotherapeutic regimen, Ox is infused in nine sessions during a six-month period. Patients will be followed for a year and nerve conduction tests, quantitative sensory evaluation, pain, quality of life and functional scales will be used to assess the impact of this strategy in the prevention of pain. If this strategy proves to work, this information will have a major impact in the cancer prognosis of patients with colorectal cancer since Ox will be able to administer in its full dose, and will not be limited by neuropathic side effects.


Condition Intervention Phase
Pain
Neuropathic Pain
Polyneuropathy
Drug: Pregabalin, Oxaliplatin
Drug: Placebo , Oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: PHASE III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pregabalin in Prevention and Reduction of Oxaliplatin-induced Painful Neuropathy

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:
  • Evaluate the efficacy [ Time Frame: base line and six months after treatment discontinuation ] [ Designated as safety issue: No ]
    Efficacy: the primary endpoint is presence of oxaliplatin-induced painful neuropathy based on Brazilian version of the Douleur Neuropathique 4 Questionnaire (DN4) 1, 2 and intensity of pain based on the numeric pain scale (11-points) of the Brief Pain Inventory.


Secondary Outcome Measures:
  • Safety [ Time Frame: base line and six months after treatment discontinuation ] [ Designated as safety issue: Yes ]
    1.Safety:Incidence and severity of adverse (AEs) and serious adverse events (SAEs); 2.Quality of life/Patient report outcomes, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC-QLQ-C30);3.Large and small fiber nerve function(Nerve conduction tests -NCT);4.Pain intensity and interference(Brief Pain Inventory-BPI);5.Depression and Anxiety (Hospital Anxiety and Depression Scale-HADS);6.Medication use(Medication Quantification Scale-MQS);7.Oxaliplatin related Neuropathy,Common Toxicity Criteria and the Total Neuropathy Scale (TNS).

  • Quality of Life [ Time Frame: base line and six months after treatment discontinuation ] [ Designated as safety issue: No ]
    This study will use the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core (EORTC-QLQ-C30) version 3.0. The EORTC-QLQ-C30 provides a QoL score on physical, role, emotional, cognitive and social functioning; a global health status; and symptom scales (pain, constipation, fatigue, and nausea and vomiting).

  • Presence of large and small fiber injury [ Time Frame: base line and six months after treatment discontinuation ] [ Designated as safety issue: Yes ]
    Peripheral nerve conduction will be assessed by the Nerve conduction tests (NCT) in the upper and lower limbs (ulnar, radial, sural, and peroneal nerves) and samll fiber function will be assessed y a quantitative sensory system protocol 7. Evaluations will take place before, at six and 12 months after study start.

  • Cancer treatment efficacy [ Time Frame: six months after treatment discontinuation ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: August 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Pregabalin Drug: Pregabalin, Oxaliplatin
Oxaliplatin will be infused according to the FLOX treatment strategy, as a regular six-month-long adjuvant treatment to colorectal cancer. Pregabalin will be administered P.O. three days before and three days after each of the nine Ox infusions. The dose will be titrated during the first Ox infusion to the highest level tolerated by the patient. The dose used in this first session will be used in the eight following sessions.
Placebo Comparator: Placebo Drug: Placebo , Oxaliplatin
Oxaliplatin will be infused according to the FLOX treatment strategy, as a regular six-month-long adjuvant treatment to colorectal cancer. Placebo will be administered P.O. three days before and three days after each of the nine Ox infusions. The dose will be titrated during the first Ox infusion to the highest level tolerated by the patient. The dose used in this first session will be used in the eight following sessions.

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  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have histologically or cytologically confirmed colorectal cancer
  • Indication of adjuvant chemotherapy regime including oxaliplatin
  • Age ≥ 18 years
  • Karnofsky performance status (KPS) ≥ 50
  • Normal neurological examination
  • Be able to understand study protocol
  • Ability to understand and the willingness to sign a written informed consent document.
  • The effects of Pregabalin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

Exclusion Criteria:

  • History of exposure to neurotoxic chemotherapy
  • Know Concomitant clinical conditions that impair peripheral nerve function,
  • Symptoms or signs suggestive of peripheral neuropathy or neuropathic pain.
  • Current peripheral neuropathy of NCI-CTCAE, version 3.0 Grade ≥ 1.
  • Inadequate organ function, evidenced by the following laboratory results within 1 week prior to randomization:
  • Serum creatinine > 2.0 mg/dL
  • Positive blood beta HCG test for women, or women breast feeding
  • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
  • History of receiving any investigational treatment within 28 days of randomization
  • Patients may not be receiving any other investigational agents.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pregabalin or known hypersensitivity to the study drug.
  • Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01450163

Locations
Brazil
Instituto do Câncer do Estado de São Paulo ICESP
São Paulo, Brazil, 01246-000
Sponsors and Collaborators
University of Sao Paulo
Pfizer
Investigators
Principal Investigator: Daniel C de Andrade, MD, PhD ICESP, Departamento de Neurologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
  More Information

No publications provided

Responsible Party: Daniel Ciampi Araujo de Andrade, Dciampi, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT01450163     History of Changes
Other Study ID Numbers: PreOx
Study First Received: April 26, 2010
Last Updated: May 22, 2014
Health Authority: Brazil: Ethics Committee
Brazil: National Health Surveillance Agency

Keywords provided by University of Sao Paulo:
Neuropathic pain
prevention
prophylaxis
chemotherapy
neuropathy
Oxaliplatin
pregabalin

Additional relevant MeSH terms:
Neuralgia
Polyneuropathies
Pain
Neurologic Manifestations
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Signs and Symptoms
Oxaliplatin
Pregabalin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on July 22, 2014