Sulfasalazine in Patients With Metastatic Colorectal Cancer

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Evaluating the change in the serum level of Ferritin [Срок оценки: 3 months]
• Evaluating the change in the serum level of Superoxide dismutase (SOD) [Срок оценки: 3 months]
• Evaluating the change in the serum level of Nuclear factor-kappa B (NF-kB) [Срок оценки: 3 months]
• Evaluating the change in the serum level of Bcl-2 associated X protein (Bax) [Срок оценки: 3 months]
• Investigating the possible efficacy of sulfasalazine through evaluation of its impact on overall response rate (ORR). [Срок оценки: 3 months]
• Investigating the possible efficacy of sulfasalazine through evaluation of its impact on disease control rate (DCR). [Срок оценки: 3 months]

Вторичные конечные точки (5)

• Evaluating the progression free survival (PFS) [Срок оценки: 12 months]
• Evaluating the one-year overall survival (1-year OS) [Срок оценки: 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)). [Срок оценки: 3 months]
• Evaluating the safety and tolerability of sulfasalazine through investigating Liver function test. [Срок оценки: 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)). [Срок оценки: 3 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Tanta University Hospital — Tanta

Публикации

• 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
• 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
• 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

Идентификаторы

NCT: NCT06134388 · Sulfasalazine 2023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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