Back to resultsNitazoxanide in Patients With Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Recruiting
Phase
Phase 3
Locations
Egypt
Study Type
Interventional
Intervention
Nitazoxanide
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Nitazoxanide
Eligibility Criteria
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
Sites / Locations
- Tanta University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Active Comparator
Arm Label
Control Group
Nitazoxanide Group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Evaluating the change in the serum level of Reduced glutathione (GSH)
Blood samples will be collected at baseline and 3 months after treatment.
Evaluating the change in the serum level of Superoxide dismutase (SOD)
Blood samples will be collected at baseline and 3 months after treatment.
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.
Evaluating the change in the serum level of Protein disulfide isomerase (PDI)
Blood samples will be collected at baseline and 3 months after treatment.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06049901
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tanta University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Nitazoxanide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
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.
Arm Title
Nitazoxanide Group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nitazoxanide
Other Intervention Name(s)
Nanazoxid
Intervention Description
Nitazoxanide is considered a broad-spectrum anti-microbial drug with a potent activity against various helminths, anaerobic bacteria and viruses.
Primary Outcome Measure Information:
Title
Investigating the possible efficacy of nitazoxanide through evaluation of its impact on overall response rate (ORR) and disease control rate (DCR).
Description
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.
Time Frame
3 months
Title
Evaluating the change in the serum level of Reduced glutathione (GSH)
Description
Blood samples will be collected at baseline and 3 months after treatment.
Time Frame
3 months
Title
Evaluating the change in the serum level of Superoxide dismutase (SOD)
Description
Blood samples will be collected at baseline and 3 months after treatment.
Time Frame
3 months
Title
Evaluating the change in the serum level of Nuclear factor-kappa B (NF-kB)
Description
Blood samples will be collected at baseline and 3 months after treatment.
Time Frame
3 months
Title
Evaluating the change in the serum level of Protein disulfide isomerase (PDI)
Description
Blood samples will be collected at baseline and 3 months after treatment.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Evaluating the one-year overall survival (1-year OS)
Description
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.
Time Frame
12 months
Title
Evaluating the progression free survival (PFS)
Description
PFS is defined as the time from randomization to investigator- assessed tumor progression. PFS will be determined as mean and median in months.
Time Frame
12 months
Title
Evaluating the safety and tolerability of nitazoxanide through investigating Liver function test (ALT (U/mL) and AST (U/mL)).
Description
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.
Time Frame
3 months
Title
Evaluating the safety and tolerability of nitazoxanide through investigating Renal function test (SCr (mg/dL), BUN (mg/dL) and eCrCl (mL/min)).
Description
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.
Time Frame
3 months
Title
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)).
Description
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.
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reham A. El-Ghoneimy, M.Sc.
Phone
+201151896761
Email
reham.elghonemy@pharm.tanta.edu.eg
Facility Information:
Facility Name
Tanta University Hospital
City
Tanta
State/Province
El-Gharbia Governorate
ZIP/Postal Code
31527
Country
Egypt
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33591350
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.
Results Reference
background
PubMed Identifier
31844249
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.
Results Reference
background
PubMed Identifier
28748751
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.
Results Reference
background
Learn more about this trial
Nitazoxanide in Patients With Metastatic Colorectal Cancer
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