Nitazoxanide in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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The aim of this study is to evaluate the potential efficacy and safety of nitazoxanide in patients with metastatic colorectal cancer.

Detailed Description
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Globally, colorectal cancer (CRC) is a major malignant tumor of the gastrointestinal tract which originates from epithelial cells of the colon and rectum. The efficacy of current cancer therapies is still limited by severe adverse effects on normal tissues and chemoresistance development. Therefore, recent efforts have been focused on the repurposing of existing drugs with good safety profiles for cancer treatment. Nitazoxanide (NTZ) is considered a broad-spectrum anti-microbial drug with a potent activity against various helminths, anaerobic bacteria and viruses. NTZ inhibited the proliferation of CRC cell lines at or below concentrations that normally exhibit anti-parasitic activity.

Official Title
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Clinical Study Evaluating the Efficacy and Safety of Nitazoxanide in Patients With Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: Nitazoxanide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of stage IV (metastatic) CRC. Staging will be performed according to the American Joint Committee on Cancer (AJCC) 8th edition and will be documented by all investigating parameters of metastatic CRC Male or female patients with age range from 18-65 years old Women of childbearing age will be required to be on acceptable forms of contraception No contraindication to chemotherapy (absence of myelosuppression) Performance status < 2 according to the Eastern Cooperative Oncology Group (ECOG) score Adequate liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < grade 2) according to the National Cancer Institute-Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v 5.0) Adequate renal function (estimated creatinine clearance (eCrCl), serum creatinine (SCr) < grade 2) according to NCI-CTCAE, v 5.0 Adequate hematological parameters (hemoglobin, erythrocytes, platelets, leukocytes and absolute neutrophil count (ANC) < grade 2 according to NCI-CTCAE, v 5.0 Exclusion Criteria: Pregnant or lactating women Patients who have known allergy to nitazoxanide or its metabolites Patients with concurrent active cancer originating from a primary site other than the colon or rectum Patients who are receiving highly plasma protein-bound drugs or drugs with extensive hepatic metabolism such as; coumarin anti-coagulants, oral hypoglycemic drugs and anti-epileptic drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control Group<br>This group will include 30 patients who will be scheduled to receive 6 cycles of 5-Fluorouracil and Oxaliplatin- based regimens every 2 weeks for 3 months. | |
| Active Comparator: Nitazoxanide Group<br>This group will include 30 patients who will be scheduled to receive 6 cycles of 5-Fluorouracil and Oxaliplatin- based regimens every 2 weeks plus nitazoxanide (500 mg orally twice daily) for 3 months. | Drug: Nitazoxanide<br>* Nitazoxanide is considered a broad-spectrum anti-microbial drug with a potent activity against various helminths, anaerobic bacteria and viruses.<br>* Other names: Nanazoxid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigating the possible efficacy of nitazoxanide through evaluation of its impact on overall response rate (ORR) and disease control rate (DCR). | Abdominal, pelvic and chest CT scanning will be performed at baseline and after 3 months. ORR and DCR will be evaluated and categorized according to the RECIST 1.1 criteria. ORR includes patients with both complete response and partial response. DCR includes patients with complete response, partial response and stable disease. Both ORR and DCR will be determined as number and percentage. | 3 months | 
| Evaluating the change in the serum level of Reduced glutathione (GSH) | Blood samples will be collected at baseline and 3 months after treatment. | 3 months | 
| Evaluating the change in the serum level of Superoxide dismutase (SOD) | Blood samples will be collected at baseline and 3 months after treatment. | 3 months | 
| Evaluating the change in the serum level of Nuclear factor-kappa B (NF-kB) | Blood samples will be collected at baseline and 3 months after treatment. | 3 months | 
| Evaluating the change in the serum level of Protein disulfide isomerase (PDI) | Blood samples will be collected at baseline and 3 months after treatment. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluating the one-year overall survival (1-year OS) | OS is defined as the time from randomization to death from any cause is OS. One-year OS will be determined as mean and median in months. | 12 months | 
| Evaluating the progression free survival (PFS) | PFS is defined as the time from randomization to investigator- assessed tumor progression. PFS will be determined as mean and median in months. | 12 months | 
| Evaluating the safety and tolerability of nitazoxanide through investigating Liver function test (ALT (U/mL) and AST (U/mL)). | These parameters will be followed up at baseline and 3 months after treatment. The reported adverse effects will be graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Effects ( NCI-CTCAE) version 5. | 3 months | 
| Evaluating the safety and tolerability of nitazoxanide through investigating Renal function test (SCr (mg/dL), BUN (mg/dL) and eCrCl (mL/min)). | These parameters will be followed up at baseline and 3 months after treatment. The reported adverse effects will be graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Effects ( NCI-CTCAE) version 5. | 3 months | 
| Evaluating the safety and tolerability of nitazoxanide through investigating Hematological parameters (hemoglobin (mg/dL), erythrocytes (cells/μL), leukocytes (cells/μL), platelets (cells/μL) and ANC (cells/μL)). | These parameters will be followed up at baseline and 3 months after treatment. The reported adverse effects will be graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Effects ( NCI-CTCAE) version 5. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nitazoxanide