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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Evaluate the efficacy
研究概览
简要总结
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.
详细描述
- OBJECTIVES
1.1. Primary Objectives
The primary objective of this study is to evaluate the efficacy of co-administration of Pregabalin during oxaliplatin infusion in reducing the appearance of both acute and late onset oxaliplatin-induced painful neuropathy in patients with colorectal cancer.
1.2. Secondary Objectives
The secondary objectives of this study are as follows:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 ≥
- •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
研究组 & 干预措施
Pregabalin
干预措施: Pregabalin, Oxaliplatin (Drug)
Placebo
干预措施: Placebo , Oxaliplatin (Drug)
结局指标
主要结局
Evaluate the efficacy
时间窗: base line and six months after treatment discontinuation
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.
次要结局
- 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)
研究者
Daniel Ciampi Araujo de Andrade
Dciampi
University of Sao Paulo