Clinical trial NCT06134388: Sulfasalazine in Patients With Metastatic Colorectal Cancer
Official title: Clinical Study Evaluating the Efficacy and Safety of Sulfasalazine in Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Sulfasalazine
mCRC
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 50
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 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.

Eligibility criteria: Inclusion Criteria:

1. 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
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. Performance status \< 2 according to the Eastern Cooperative Oncology Group (ECOG) score
5. No contraindication to chemotherapy (absence of myelosuppression)
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 with concurrent active cancer originating from a primary site other than the colon or rectum
3. Patients who have known allergy to sulfasalazine or its metabolites
4. Patients with nephrolithiasis, severe vomiting or severe diarrhea
5. Patients who are receiving highly plasma protein-bound drugs or drugs with extensive hepatic metabolism such as; coumarin anti-coagulants
6. Patients with intestinal or urinary obstruction
7. Patients with known glucose-6-phosphate dehydrogenase deficiency or porphyria
8. Ongoing treatment with sulfasalazine or mesalamine for ulcerative colitis or rheumatoid arthritis

Primary outcomes:
measure: Evaluating the change in the serum level of Ferritin
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 Bcl-2 associated X protein (Bax)
timeFrame: 3 months
measure: Investigating the possible efficacy of sulfasalazine through evaluation of its impact on overall response rate (ORR).
timeFrame: 3 months
measure: Investigating the possible efficacy of sulfasalazine through evaluation of its impact on disease control rate (DCR).
timeFrame: 3 months
Secondary outcomes:
measure: Evaluating the progression free survival (PFS)
timeFrame: 12 months
measure: Evaluating the one-year overall survival (1-year OS)
timeFrame: 12 months
measure: 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)).
timeFrame: 3 months
measure: Evaluating the safety and tolerability of sulfasalazine through investigating Liver function test.
timeFrame: 3 months
measure: 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)).
timeFrame: 3 months
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta University Hospital
state: El-Gharbia Governorate
Study officials:
References:
citation: Ma MZ, Chen G, Wang P, Lu WH, Zhu CF, Song M, Yang J, Wen S, Xu RH, Hu Y, Huang P. Xc- inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism. Cancer Lett. 2015 Nov 1;368(1):88-96. doi: 10.1016/j.canlet.2015.07.031. Epub 2015 Aug 5.
citation: Yin L, Liu P, Jin Y, Ning Z, Yang Y, Gao H. Ferroptosis-related small-molecule compounds in cancer therapy: Strategies and applications. Eur J Med Chem. 2022 Dec 15;244:114861. doi: 10.1016/j.ejmech.2022.114861. Epub 2022 Oct 22.
citation: Narang VS, Pauletti GM, Gout PW, Buckley DJ, Buckley AR. Sulfasalazine-induced reduction of glutathione levels in breast cancer cells: enhancement of growth-inhibitory activity of Doxorubicin. Chemotherapy. 2007;53(3):210-7. doi: 10.1159/000100812. Epub 2007 Mar 15.