Sulfasalazine in Patients With Metastatic Colorectal Cancer

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

Detailed Description
-----------------
Sulfasalazine is an anti-inflammatory drug that is indicated for treatment of ulcerative colitis and rheumatoid arthritis. Sulfasalazine decreased the risk of ulcerative colitis-related colorectal cancer through its anti-inflammatory effect and induction of oxidative stress in cancer cells. Furthermore, intact sulfasalazine, but not its metabolites, inhibited the growth and metastasis various cancers.

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

Conditions
-----------------
Metastatic Colorectal Cancer

Intervention / Treatment
-----------------
* Drug: Sulfasalazine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed diagnosis of stage IV (metastatic) colorectal cancer. 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 colorectal cancer 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 Performance status < 2 according to the Eastern Cooperative Oncology Group (ECOG) score No contraindication to chemotherapy (absence of myelosuppression) 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 with concurrent active cancer originating from a primary site other than the colon or rectum Patients who have known allergy to sulfasalazine or its metabolites Patients with nephrolithiasis, severe vomiting or severe diarrhea Patients who are receiving highly plasma protein-bound drugs or drugs with extensive hepatic metabolism such as; coumarin anti-coagulants Patients with intestinal or urinary obstruction Patients with known glucose-6-phosphate dehydrogenase deficiency or porphyria Ongoing treatment with sulfasalazine or mesalamine for ulcerative colitis or rheumatoid arthritis

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 25 patients who will be scheduled to receive 6 cycles of 5-Fluorouracil and Oxaliplatin- based regimens every 2 weeks for 3 months. | |
| Active Comparator: Sulfasalazine Group<br>This group will include 25 patients who will be scheduled to receive 6 cycles of 5-Fluorouracil and Oxaliplatin- based regimens every 2 weeks plus sulfasalazine (1 gram orally twice daily) for 3 months. | Drug: Sulfasalazine<br>* Sulfasalazine is an anti-inflammatory drug that is indicated for treatment of ulcerative colitis and rheumatoid arthritis.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluating the change in the serum level of Ferritin | 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 Bcl-2 associated X protein (Bax) | Blood samples will be collected at baseline and 3 months after treatment. | 3 months | 
| Investigating the possible efficacy of sulfasalazine through evaluation of its impact on overall response rate (ORR). | Abdominal, pelvic and chest CT scanning will be performed at baseline and after 3 months. ORR will be evaluated and categorized according to the RECIST 1.1 criteria. ORR includes patients with both complete response and partial response. ORR will be determined as number and percentage. | 3 months | 
| Investigating the possible efficacy of sulfasalazine through evaluation of its impact on disease control rate (DCR). | Abdominal, pelvic and chest CT scanning will be performed at baseline and after 3 months. DCR will be evaluated and categorized according to the RECIST 1.1 criteria. DCR includes patients with complete response, partial response and stable disease. DCR will be determined as number and percentage. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 safety and tolerability of sulfasalazine through investigating Hematological parameters (hemoglobin (mg/dL), erythrocytes (cells/μL), leukocytes (cells/μL), platelets (cells/μL) and absolute neutrophil count (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 | 
| Evaluating the safety and tolerability of sulfasalazine through investigating Liver function test. | 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 sulfasalazine through investigating Renal function test (serum creatinine (mg/dL), blood urea nitrogen (mg/dL) and creatinine clearance (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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sulfasalazine, mCRC