Clinical trial NCT07025005: Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Peripheral Neuropathy
Multiple Myeloma, Neoplasms
Keywords: peripheral neuropathy
multiple myeloma
bortezomib induced peripheral neuropathy (BIPN)
Fenofibrate
VRd protocol
lenalidomide
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2025-06-17
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: At admission, patients will be randomized through sealed envelopes method into two groups to receive either the VRd regimen or the VRd regimen plus fenofibrate 160 mg:

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.
Primary purpose: PREVENTION

Brief summary: 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:

1. 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.
2. 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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.
timeFrame: 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.
Secondary outcomes:
measure: The change in serum levels of the measured biological markers BDNF and NFL.
timeFrame: The assessment of serum level of the biological markers: Brain -derived neurotrophic factor (BDNF) and Neuro-filament light chain (NfL) will be done at the baseline and after the last VRd cycle (the 6th cycle) ( the duration of each cycle is 28 days).
Other outcomes:
Locations:
city: Damanhur
country: Egypt
facility: Damanhur Oncology Center
state: El- Behira
city: Tanta
country: Egypt
facility: Tanta University
state: El-Gharbya
Study officials:
affiliation: clinical pharmacy departement - Faculty of Pharmacy - Tanta University
name: Ashraf M Alaa, BSc of clinical pharmacy
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jin L, Hua H, Ji Y, Jia Z, Peng M, Huang S. Anti-inflammatory role of fenofibrate in treating diseases. Biomol Biomed. 2023 May 1;23(3):376-391. doi: 10.17305/bb.2022.8534.
citation: Azoulay D, Lavie D, Horowitz N, Suriu C, Gatt ME, Akria L, Perlman R, Braester A, Ben-Yehuda D. Bortezomib-induced peripheral neuropathy is related to altered levels of brain-derived neurotrophic factor in the peripheral blood of patients with multiple myeloma. Br J Haematol. 2014 Feb;164(3):454-6. doi: 10.1111/bjh.12624. Epub 2013 Oct 25. No abstract available.
citation: Cebulla N, Schirmer D, Runau E, Flamm L, Gommersbach S, Stengel H, Zhou X, Einsele H, Reinhold AK, Rogalla von Bieberstein B, Zeller D, Rittner H, Kortum KM, Sommer C. Neurofilament light chain levels indicate acute axonal damage under bortezomib treatment. J Neurol. 2023 Jun;270(6):2997-3007. doi: 10.1007/s00415-023-11624-2. Epub 2023 Feb 18.
citation: Caillaud M, Patel NH, White A, Wood M, Contreras KM, Toma W, Alkhlaif Y, Roberts JL, Tran TH, Jackson AB, Poklis J, Gewirtz DA, Damaj MI. Targeting Peroxisome Proliferator-Activated Receptor-alpha (PPAR- alpha) to reduce paclitaxel-induced peripheral neuropathy. Brain Behav Immun. 2021 Mar;93:172-185. doi: 10.1016/j.bbi.2021.01.004. Epub 2021 Jan 9.
citation: Esmaeili MA, Yadav S, Gupta RK, Waggoner GR, Deloach A, Calingasan NY, Beal MF, Kiaei M. Preferential PPAR-alpha activation reduces neuroinflammation, and blocks neurodegeneration in vivo. Hum Mol Genet. 2016 Jan 15;25(2):317-27. doi: 10.1093/hmg/ddv477. Epub 2015 Nov 24.
citation: Yamamoto S, Egashira N. Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy. Int J Mol Sci. 2021 Jan 17;22(2):888. doi: 10.3390/ijms22020888.