The Possible Protective Effect of Pentoxifylline Against Chemotherapy Induced Toxicities in Patients With Colorectal Cancer
试验速览
- 阶段
- 早期 1 期
- 状态
- Enrolling By Invitation
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- variation of 12-item neurotoxicity questionnaire (Ntx- 12) total score
研究概览
简要总结
This study aims to:
- Evaluate the possible protective effect of pentoxifylline against oxaliplatin induced peripheral neuropathy and chemotherapy induced mucositis in patients with stage II and stage III colorectal cancer.
This study will be a randomized placebo controlled parallel study.48 patients with colorectal cancer will be randomized to 2 groups:
Group I (control group; n=24) which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. Group II (Pentoxiphylline group; n=24) which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily.
Blood sample collection and biochemical assessment:
- Malondialdehyde (MDA) as oxidative stress marker (colorimetry).
- Tumor necrosis factor alfa (TNF-α) as pro inflammatory marker (ELISA).
- Neurotensin (NT) as a potential marker for neuropathic pain (ELISA).
- Citrulline as a biomarker for mucositis (ELISA).
Clinical assessment of oxaliplatin induced neuropathy will be done through:
The assessment of the severity of neuropathic pain through "Brief Pain Inventory-Short Form" at baseline and by the end of every two chemotherapy cycles.
The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) for grading of neuropathy every 2 cycles. The use of Neurotoxicity- 12 item questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group at baseline and by the end of every two chemotherapy cycles).
Mucositis will be assessed at baseline and by the end of every two chemotherapy cycles through the use of common terminology criteria for adverse events "CTCAE, version 5.00, 2017
详细描述
This study aims to:
- Evaluate the possible protective effect of pentoxifylline against oxaliplatin induced peripheral neuropathy and chemotherapy induced mucositis in patients with stage II and stage III colorectal cancer.
This study will be a randomized placebo controlled parallel study.48 patients with colorectal cancer will be randomized to 2 groups:
Group I (control group; n=24) which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily. Group II (Pentoxiphylline group; n=24) which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily.
Blood sample collection and biochemical assessment:
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
- None
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
- •- Patients with histologically confirmed diagnosis of stage II and stage III colorectal cancer.
- •Patients who will be scheduled to receive FOLFOX-6 regimen.
- •Patients with no contraindication to chemotherapy.
- •Males and females aged ≥ 18 years old.
- •Adequate baseline hematologic values (absolute neutrophilic count ≥ 1.5
- •× 109/L, platelet count ≥ 100 × 109/L and hemoglobin level ≥ 10 g/dl).
- •Patients with adequate renal function (serum creatinine < 1.5 mg/dL and Creatinine clearance (ClCr) ˃ 45 mL/min).
- •Patients with adequate liver function (serum bilirubin < 1.5 mg/dl).
- •Patients with performance status < 2 according to Eastern Cooperative Oncology Group (ECOG) score.
排除标准
- •- Children < 18 years old.
- •Prior exposure to neurotoxic chemotherapy (oxaliplatin, cisplatin, vincristine, paclitaxel, docetaxel or Isoniazid) for at least 6 months prior the study treatment.
- •Evidence of pre-existing peripheral neuropathy resulting from another reason (diabetes, brain tumor or brain trauma).
- •Patients with diabetes and other conditions that predispose to neuropathy as hypothyroidism, autoimmune diseases or hepatitis C.
- •History of known allergy to oxaliplatin or other platinum agents.
- •Patients with other inflammatory diseases (rheumatoid arthritis and ulcerative colitis) or stressful conditions (obesity class 2 and 3, smoking).
- •Concomitant use of multivitamins (vitamins E, C and A), tricyclic antidepressants or other neuro-protective medications (gabapentin, lamotrigine, carbamazepine and phenytoin, etc...).
- •Concurrent active cancer originating from a primary site other than colon or rectum.
- •Patients on blood thinning agents
- •Pregnant and breastfeeding women
研究组 & 干预措施
Group 1 placebo
n=24 which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily.
干预措施: Placebo (Drug)
Group 1 placebo
n=24 which will receive 12 cycles of FOLFOX-6 regimen plus placebo tablets twice daily.
干预措施: FOLFOX-6 regimen (Drug)
Group 2 pentoxifylline
n=24 which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily.
干预措施: Pentoxifylline (Drug)
Group 2 pentoxifylline
n=24 which will receive FOLFOX-6 regimen in addition to pentoxifylline 400 mg twice daily.
干预措施: FOLFOX-6 regimen (Drug)
结局指标
主要结局
variation of 12-item neurotoxicity questionnaire (Ntx- 12) total score
时间窗: 6 months
the Ntx-12 questionnaire is comprised of 12 statements intended to measure the severity and impact of peripheral sensory neuropathy on patients' lives. Patients will be instructed to complete the Arabic version of the Ntx-12 and choose the number corresponding to how true each statement was for them using a likert-type scale, with 0 indicating not at all; 1, a little bit; 2, somewhat; 3, quite a bit; and 4, very much
variation in grades of mucositis
时间窗: 6 months
Mucositis will be assessed through the use of common terminology criteria for adverse events "CTCAE, version 5.00, 2017". Grade (1) is Asymptomatic or mild symptoms; intervention not indicated. Grade (2) is Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated. Grade (3) is Severe pain, interfering with oral intake. Grade (4) is Life-threatening consequences; urgent intervention indicated. Grade (5) is Death.
percentage of patients with peripheral sensory neuropathy grade ≥ 2
时间窗: 6 months
Grading according to National Cancer Institute Common Terminology. there are 5 grades; Grade (1) is asymptomatic may be accompanied by loss of tendon reflex or paresthesia. Grade (2) is moderate symptoms which limit instrumental activities of daily life Grade (3) is severe symptoms which limit self-care activates of daily life. Grade (4) is life threatening consequences or urgent intervention indicated. Grade (5) is death. Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017)
次要结局
- Change in the biological marker Malondialdehyde(6 months)
- Change in the biological marker Neurotensin(6 months)
- Change in the biological marker Citrulline(6 months)
- Change in the biological marker Tumor necrosis factor alfa(6 months)
研究者
Mostafa Tarek Aboelnoor
Principal Investigator
Tanta University