Clinical Study to Evaluate the Possible Role of Fenofibrate in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone Protocol in the Treatment of Patients With Multiple Myeloma
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- The change in percentage of patients with peripheral neuropathy grade ≥ 2 with the variation of both 12-item neurotoxicity questionnaire (Ntx-12) total score and NCI-CTCAE, v5.
研究概览
简要总结
This study aims at evaluating the possible beneficial role of Fenofibrate in attenuating the peripheral neuropathy associated with bortezomib (velcade), lenalidomide (revlimid), and dexamethasone (VRd) regimen in newly diagnosed multiple myeloma patients.The study aims to asses VRd protocol induced peripheral neuropathy through:
- The implication of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 5, 2017) and The use of Neurotoxicity-12 items questionnaire score (Ntx-12) from the validated Functional Assessment of Cancer Therapy/Gynecologic Oncology Group "FACT/GOG-Ntx-12 for grading of neuropathy at baseline and by the end of every two VRd cycles.
- The assessment of biological markers:
Brain -derived neurotrophic factor (BDNF) and Neuro-filament light chain (NfL). through comparing two groups: Group one: (Control group; n=22): which will receive 6 cycles of VRd regimen (each cycle will be given every 28 days).
Group two: (Fenofibrate group; n=22): which will receive the same regimen plus Fenofibrate 160 mg once daily.
详细描述
Multiple myeloma is considered an incurable disease so several regimens are available for the management of multiple myeloma.
Among these regimens there is the bortezomib, lenalidomide and dexamethasone (RVd or VRd) regimen which is the preferred induction regimen for most patients with newly diagnosed multiple myeloma (NDMM).
Bortezomib has hematologic and non-hematologic adverse reactions. From the non-hematologic adverse reactions there is the bortezomib-induced peripheral neuropathy (BIPN) that remains the most intractable common adverse reactions that occur during bortezomib treatment with no recommended therapies available for preventing or treating existing BIPN.
Fenofibrate a peroxisome proliferator-activated receptor-alpha (PPARα) agonist that is widely used in the management of hypercholesterolemia and hypertriglyceridemia has been proposed as a key lipid metabolism modulator and regulator of inflammation.
Preclinical studies showed that treatment with fenofibrate partially reversed and prevented the development of mechanical and cold hypersensitivity induced by paclitaxel through the regulation of peroxisome proliferator-activated receptor-alpha (PPAR-α) expression and decrease neuroinflammation in the dorsal root ganglia (DRG) without decreasing the antitumoral effect of paclitaxel.
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
- Single (Participant)
盲法说明
sealed envelopes method
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
- •Age ≥ 18 years old.
- •Newly diagnosed MM patients according to the revised International Myeloma Working Group Diagnostic Criteria for the diagnosis of Multiple Myeloma (IMWG).
- •Patients being treated by bortezomib-based VRd chemotherapy regimen.
- •Patients with performance status <2 according to Eastern Cooperative Oncology Group (ECOG) score.
- •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 liver function (serum bilirubin < 1.2 mg/dl) and adequate renal function (serum creatinine < 1.5 mg/d).
排除标准
- •Patients with prior exposure to neurotoxic agents (Cis-platin, vincristine, taxanes, foscarnet, INH, etc..) in the last 6 months.
- •Concomitant use of antioxidant vitamins (vitamin A, C, E), anticonvulsants, tricyclic antidepressants, other medications used for neuropathic pain (gabapentin, lamotrigine, carbamazepine).
- •Preexisting peripheral neuropathy resulting from other causes such as diabetes and brain disorders, hypothyroidism, autoimmune diseases, hepatitis C.
- •Patients with inflammatory diseases (ulcerative colitis, rheumatoid arthritis).
- •Patients with conditions associated with oxidative stress (smoking, tuberculosis, comorbid obesity).
- •Patients with active liver disease (cirrhosis, fatty liver, hepatitis C, etc..).
- •Patients with myopathy.
- •Patients with other malignancies.
- •Patients with renal impairment, including those with end-stage renal disease and those receiving dialysis.
- •Patients with Gallbladder disease and gallstones.
- •Pregnant and breast-feeding women.
- •Patients with Known allergy to the fenofibrates.
- •Concurrent use of statin, colchicine, Ciprofibrate, idelalisib, enzyme inducers (phenytoin, phenobarbitone, carbamazepine,…), enzyme inhibitors (ketoconazole, clarithromycin,…), drugs with high plasma protein binding capacity (Sulfonamides, valproate, oral hypoglycemic, warfarin,…) to avoid potential pharmacodynamics and pharmacokinetic drug interactions.
研究组 & 干预措施
Fenofibrate group
22 participants will receive 6 cycles of (VRd) regimen plus Fenofibrate 160 mg tablet once daily during the period of the 6 cycles.
干预措施: Bortezomib + Lenalidomide + Dexamethasone + Fenofibrate 160 mg tablet (Drug)
Control group
22 participants will receive 6 cycles of VRd regimen (each cycle will be given for 28 days)
干预措施: Bortezomib + Lenalidomide + Dexamethasone (Drug)
结局指标
主要结局
The change in percentage of patients with peripheral neuropathy grade ≥ 2 with the variation of both 12-item neurotoxicity questionnaire (Ntx-12) total score and NCI-CTCAE, v5.
时间窗: The use of NCI-CTCAE, Version 5, 2017 and "FACT/GOG-Ntx-12" for the grading of peripheral neuropathy will be done at the baseline and by the end of every two VRd cycles ( the duration of each cycle is 28 days) during the 6 VRd cycles duration.
The change in percentage of patients with peripheral neuropathy grade ≥ 2 using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5 (NCI-CTCAE, v5) ( where the higher the score the more severity of the peripheral neuropathy) and the use of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 12 Item Version (FACT/GOG-NTX-12) to assess (where the higher the score, the better the Quality of life).
次要结局
- The change in serum levels of the measured biological markers Brain -derived neurotrophic factor (BDNF) and Neuro-filament light chain (NfL).(The assessment of serum level of the biological markers Brain -derived neurotrophic factor (ng/ml) and Neuro-filament light chain (pg/ml) will be done at the baseline and within 1 week after the 6th VRd cycle ( the duration of each cycle is 28 days).)
研究者
Ashraf Mohamed Alaa Mokhtar
Instructor at Clinical Pharmacy Department -Faculty of Pharmacy- Tanta University
Tanta University