Clinical trial NCT05680870: The Possible Protective Role of Omeprazole Against Oxaliplatin Induced Neuropathy in Cancer Patients
Official title: The Possible Protective Role of Omeprazole Against Oxaliplatin Induced Neuropathy in Patients With Cancer Treated With Oxaliplatin-fluorouracil Chemotherapy Protocols
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chemotherapy Induced Peripheral Neuropathy
Keywords: Peripheral neuropathy
Colorectal cancer
Pancreatic cancer
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2023-01-11
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 46 participants will be classified into 2 arms : intervention arm will receive omeprazole plus chemotherapy Control arm will receive chemotherapy only
Primary purpose: PREVENTION

Brief summary: Oxaliplatin(OXA) chemotherapy protocols are used in treatment of cancers like colorectal (CRC) and pancreatic cancer. OXA causes peripheral neuropathy which is considered treatment limiting factor. In recent studies, it shows that omeprazole(OME) has antioxidant effect and can inhibit organic cation transporter 2 (OCT2) in kidney. So OME can protect against peripheral neuropathy induced by OXA through oxidative stress . Also OME activates extracellular-signal-regulated kinase(ERK) / mitogen activated protein kinase ( MAPK) pathway, so improves demyelinating symptoms.

Detailed description: Randomized controlled parallel study

Forty-six patients with pancreatic cancer or CRC who receive OXA 85mg/m2 in their protocols scheduled as a cycle every two consecutive weeks for 6 months to receive 12 cycles. Patients will be recruited from Clinical Oncology and Nuclear Medicine Department, Mansoura University Hospital, Mansoura, Egypt. The patients will be randomized using sealed envelope method into two groups:

According to the results of previous studies, the total number of subjects required detecting the effect of neuro-protective drugs in patients received chemotherapy with 5% significance and 80% power and attrition rate equal to 15% was 41 . In this context, during the current study, a total sample size 42 patients in both arms will be sufficient to provide a good power to detect the effect. Assuming that the attrition rate will be 10% the initial sample size will be 46 patients in both arms.

Assessment of patient adherence and evaluation of drug safety The medication will be provided on biweekly intervals and the participants adherence will be assessed through counting the pills and by medications refilling rate. Participants will also followed-up by telephone calls and through direct meetings during chemotherapy cycles to assess their adherence and report any drugs related adverse effects using adverse drug reactions reporting form the adverse effects will be also collected through patients' laboratory data and patient sheet. The patients will be asked about any adverse effects related to study medication. Patients will be considered non-adherent and excluded from the study if consumed less than 90% of study medication at any month of the study duration.

Statistical analysis - Statistical analysis will be done by the statistical software package version 25 . Data will be tested for normality using Kolmogorov-Smirnov and Shapiro wilk tests. Normally distributed data will be analyzed using paired and un-paired t-test. Non normally distributed data will be compared using Mann-Whitney U test. Also, Mann-Whitney U test will be used to compare non-parametric data between the two arms including the neuropathy grading and the Neurotoxicity-12(NTX-12) total scores. Categorical data will be computed by Chi-square test. - Fisher exact test will be used to analyze the reported adverse effects. - Correlation between variables will be analyzed by Pearson or spearman correlation what appropriate. - The significance level was set at p\<0.05.

Eligibility criteria: Inclusion Criteria:

* Recently diagnose cases with colorectal (CRC)and pancreatic cancers (males and females) ≥ 18 years old, and ≤ 65 years old.
* Patients who will scheduled to receive modified FOLFOX-4,6,7 (OXA, Leucovorin, and 5-fluorouracil) or mFOLFIRINOX (OXA, irinotecan,leucovorin, and 5-Fluorouracil) for 12 cycles.
* Patients with performance status 0-2 according to Eastern Cooperative Oncology Group (ECOG) Score.

Exclusion Criteria:

* Evidence of pre-existing peripheral neuropathy resulting from another reason (documented patients with brain tumor, brain trauma, seizures or any other neuropathic disorder).
* CRC patients receiving protocols containing capecitabine.
* Diabetic patients.
* Documented Patients with lupus (SLE), or any other autoimmune disease.
* Documented Patients with osteoporosis or fractures.
* Prior exposure to neurotoxic chemotherapy for at least 6 months prior to the study.
* Concomitant use of other neuroprotective medications (gabapentin, lamotrigine, phenytoin, tricyclic antidepressants, etc.,).
* Patients taking medications that omeprazole can interact with or affect their metabolism, such as (digoxin, ketoconazole, methotrexate, clopidogrel, marevan, etc.,).
* Pregnant and breastfeeding women.
* Patients with abnormal renal function (S.cr \> 1.5 mg/dl or crcl \< 45 ml/min).
* Patients with liver diseases (serum bilirubin \> 1.5 mg/dl / Alanine transaminase, Aspartate transaminase \> 2-4 ULN).
* Smokers or documented patients with condition associated with oxidative stress.

Primary outcomes:
measure: Acute peripheral neuropathy
timeFrame: After the first intervention by 2 weeks of the first chemotherapy cycle ( each cycle is two days every two weeks), and through the study average for six months
measure: Chronic peripheral neuropathy
timeFrame: After the end of 12 chemotherapy cycles ( after six months of interventions)
Secondary outcomes:
measure: Malonaldehyde
timeFrame: After 3 months of treatment
measure: Neurotensin
timeFrame: After 3 months of treatment
measure: OCT
timeFrame: After 3 months of treatment
Other outcomes:
Locations:
Study officials:
affiliation: Professor of clinical pharmacy , faculty of pharmacy, Tanta university
name: Sahar K Hegazy, Professor
role: STUDY_DIRECTOR
References: