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

NCT01450163 | Completed Phase 3 DMC

• 1 other identifier: PreOx
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain; Neuropathic Pain; Polyneuropathy

Keywords

Neuropathic pain; prevention; prophylaxis; chemotherapy; neuropathy; Oxaliplatin; pregabalin

Outcome Measures

Primary Outcomes (1)

• Evaluate the efficacy

  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.

  base line and six months after treatment discontinuation

Secondary Outcomes (4)

• Safety

  base line and six months after treatment discontinuation

• Quality of Life

  base line and six months after treatment discontinuation

• Presence of large and small fiber injury

  base line and six months after treatment discontinuation

• Cancer treatment efficacy

  six months after treatment discontinuation

Study Arms (2)

Pregabalin

ACTIVE COMPARATOR

Drug: Pregabalin, Oxaliplatin

Placebo

PLACEBO COMPARATOR

Drug: Placebo , Oxaliplatin

Interventions

Pregabalin, Oxaliplatin DRUG

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.

Pregabalin

Placebo , Oxaliplatin DRUG

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.

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sao Paulo: lead
• Pfizer: collaborator

Study Sites (1)

Instituto do Câncer do Estado de São Paulo ICESP

São Paulo, 01246-000, Brazil

Location

Related Publications (1)

• de Andrade DC, Jacobsen Teixeira M, Galhardoni R, Ferreira KSL, Braz Mileno P, Scisci N, Zandonai A, Teixeira WGJ, Saragiotto DF, Silva V, Raicher I, Cury RG, Macarenco R, Otto Heise C, Wilson Iervolino Brotto M, Andrade de Mello A, Zini Megale M, Henrique Curti Dourado L, Mendes Bahia L, Lilian Rodrigues A, Parravano D, Tizue Fukushima J, Lefaucheur JP, Bouhassira D, Sobroza E, Riechelmann RP, Hoff PM; PreOx Workgroup; Valerio da Silva F, Chile T, Dale CS, Nebuloni D, Senna L, Brentani H, Pagano RL, de Souza AM. Pregabalin for the Prevention of Oxaliplatin-Induced Painful Neuropathy: A Randomized, Double-Blind Trial. Oncologist. 2017 Oct;22(10):1154-e105. doi: 10.1634/theoncologist.2017-0235. Epub 2017 Jun 26.

  PMID: 28652279 DERIVED

MeSH Terms

Conditions

Pain; Neuralgia; Polyneuropathies

Interventions

Pregabalin; Oxaliplatin

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Coordination Complexes

Study Officials

• Daniel C de Andrade, MD, PhD

  ICESP, Departamento de Neurologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 26, 2010
• First Posted: October 12, 2011
• Study Start: August 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

BR (1)