Clinical trial NCT06049901: Nitazoxanide in Patients With Metastatic Colorectal Cancer
Official title: Clinical Study Evaluating the Efficacy and Safety of Nitazoxanide in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Nitazoxanide
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2023-09-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Male or female patients with age range from 18-65 years old
3. Women of childbearing age will be required to be on acceptable forms of contraception
4. No contraindication to chemotherapy (absence of myelosuppression)
5. Performance status \< 2 according to the Eastern Cooperative Oncology Group (ECOG) score
6. 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)
7. Adequate renal function (estimated creatinine clearance (eCrCl), serum creatinine (SCr) \< grade 2) according to NCI-CTCAE, v 5.0
8. Adequate hematological parameters (hemoglobin, erythrocytes, platelets, leukocytes and absolute neutrophil count (ANC) \< grade 2 according to NCI-CTCAE, v 5.0

Exclusion Criteria:

1. Pregnant or lactating women
2. Patients who have known allergy to nitazoxanide or its metabolites
3. Patients with concurrent active cancer originating from a primary site other than the colon or rectum
4. 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

Primary outcomes:
measure: Investigating the possible efficacy of nitazoxanide through evaluation of its impact on overall response rate (ORR) and disease control rate (DCR).
timeFrame: 3 months
measure: Evaluating the change in the serum level of Reduced glutathione (GSH)
timeFrame: 3 months
measure: Evaluating the change in the serum level of Superoxide dismutase (SOD)
timeFrame: 3 months
measure: Evaluating the change in the serum level of Nuclear factor-kappa B (NF-kB)
timeFrame: 3 months
measure: Evaluating the change in the serum level of Protein disulfide isomerase (PDI)
timeFrame: 3 months
Secondary outcomes:
measure: Evaluating the one-year overall survival (1-year OS)
timeFrame: 12 months
measure: Evaluating the progression free survival (PFS)
timeFrame: 12 months
measure: Evaluating the safety and tolerability of nitazoxanide through investigating Liver function test (ALT (U/mL) and AST (U/mL)).
timeFrame: 3 months
measure: Evaluating the safety and tolerability of nitazoxanide through investigating Renal function test (SCr (mg/dL), BUN (mg/dL) and eCrCl (mL/min)).
timeFrame: 3 months
measure: 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)).
timeFrame: 3 months
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta University Hospital
state: El-Gharbia Governorate
Study officials:
References:
citation: Biller LH, Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021 Feb 16;325(7):669-685. doi: 10.1001/jama.2021.0106.
citation: Ripani P, Delp J, Bode K, Delgado ME, Dietrich L, Betzler VM, Yan N, von Scheven G, Mayer TU, Leist M, Brunner T. Thiazolides promote G1 cell cycle arrest in colorectal cancer cells by targeting the mitochondrial respiratory chain. Oncogene. 2020 Mar;39(11):2345-2357. doi: 10.1038/s41388-019-1142-6. Epub 2019 Dec 16.
citation: Shakya A, Bhat HR, Ghosh SK. Update on Nitazoxanide: A Multifunctional Chemotherapeutic Agent. Curr Drug Discov Technol. 2018;15(3):201-213. doi: 10.2174/1570163814666170727130003.