Sulfasalazine in Patients With Metastatic Colorectal Cancer

NCT06134388 | Recruiting Phase 3

• 1 other identifier: Sulfasalazine 2023
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Metastatic Colorectal Cancer

Keywords

Sulfasalazine; mCRC

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Evaluating the progression free survival (PFS)

  12 months

• Evaluating the one-year overall survival (1-year OS)

  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)).

  3 months

• Evaluating the safety and tolerability of sulfasalazine through investigating Liver function test.

  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)).

  3 months

Study Arms (2)

Control Group

NO INTERVENTION

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.

Sulfasalazine Group

ACTIVE COMPARATOR

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

Interventions

Sulfasalazine DRUG

Sulfasalazine is an anti-inflammatory drug that is indicated for treatment of ulcerative colitis and rheumatoid arthritis.

Sulfasalazine Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

Tanta University Hospital

Tanta, El-Gharbia Governorate, 31527, Egypt

RECRUITING

Related Publications (3)

• 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.

  PMID: 26254540 BACKGROUND

• 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.

  PMID: 36332549 BACKGROUND

• 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.

  PMID: 17356269 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Sulfasalazine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Central Study Contacts

Reham A. El-Ghoneimy, M.Sc in Clinical Pharmacy

CONTACT

+201151896761; reham.elghonemy@pharm.tanta.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer of Clinical Pharmacy, Faculty of Pharmacy, Tanta University

Study Record Dates

• First Submitted: November 5, 2023
• First Posted: November 18, 2023
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)