Effect of Silymarin in Metastatic Colorectal Cancer Patients

Metastatic Colorectal Cancer Clinical Trial

Official title:

The Possible Anticancer Effect of Silymarin in Patients With Metastatic Colorectal Cancer Receiving Chemotherapy.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05631041
• Other study ID #: Silymarin in Colorectal Cancer
• Status: Recruiting
• Phase: Phase 3
• Start date: December 31, 2022
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: Tanta University
• Contact: Shimaa Yassin, pharmacist
• Phone: 01003228294
• Email: shaimaa150849[@]pharm.tanta.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

this work is aim to assess the antitumor effect of silymarin in patients with metastatic colorectal cancer receiving chemotherapy with or without target therapy (Bevacizumab).

Description:

Colorectal cancer (CRC) ranks as the third most common cancer globally and second in terms of mortality . Although CRC incidence rates are higher in high-income compared with low-to-middle-income countries (LMICs), mortality is higher in LMICs.

Extensive research within the last decade has shown that silymarin can suppress the proliferation of a variety of tumor cells; this is accomplished through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors, down-regulation of anti- apoptotic gene products, inhibition of cell-survival kinases and inhibition of inflammatory transcription factors (e.g., Nuclear Factor- kappa B) through suppression of Nuclear Factor- kappa B-regulated gene products, including Cyclooxygenase-2, Lipoxygenase, Tumor necrosis factor and Interleukin-1. Silymarin can also down-regulate gene products involved in the proliferation of tumor cells (Epidermal Growth Factor Receptor, Cyclooxygenase-2), invasion (Matrix metallopeptidase 9), angiogenesis (Vascular Endothelial growth Factor) and metastasis (adhesion molecules). Silymarin was reported to alter the expression of apoptosis-related proteins including BCL2 associated X protein to induce apoptosis in human gastric cancer cells in a concentration-dependent manner. Silymarin has also been shown to sensitize tumors to chemotherapeutic agents through down-regulation of the Multidrug resistance protein and other mechanisms. In addition to its chemo-preventive effects, silymarin exhibits antitumor activity against human tumors in rodents. so we aim to assess the antitumor activity of silymarin in metastatic colorectal cancer patients receiving chemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: December 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• - Patients with histologically and/or radiologically confirmed diagnosis of metastatic colorectal carcinoma.

• Patients who received FOLFOX or XELOX as first line chemotherapy

• Both genders.

• Age =18 years old.

• Performance status 0-1 according to the Eastern Cooperative Oncology Group (ECOG).

• Patients with adequate hematologic parameters (white blood cell count

=3000/mm3, granulocytes =1500/mm3, platelets =100,000/mm3, hemoglobin = 8 gm/l).

• Patients with adequate renal functions (serum creatinine =1.5 mg/dL).

• Patients with adequate hepatic functions (bilirubin =1.5 mg/dL or albumin =3 g/dL).

Exclusion Criteria:

• - Patients with active liver diseases (chronic viral hepatitis, autoimmune hepatitis, alcoholic hepatitis, Wilson's disease, hemochromatosis, or cirrhosis).

• Patients with a history of other malignancy.

• Patients with brain metastasis.

• Patients with active infection.

• Patients with RAS wild type cancer.

• Patients on chronic use of corticosteroids.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• Silymarin
participants in silymarin group will receive silymarin 140 mg once daily.

Locations

Country	Name	City	State
Egypt	faculty of Pharmacy , Tanta University	Tanta

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (5)

Abou-Zeid AA, Khafagy W, Marzouk DM, Alaa A, Mostafa I, Ela MA. Colorectal cancer in Egypt. Dis Colon Rectum. 2002 Sep;45(9):1255-60. doi: 10.1007/s10350-004-6401-z. — View Citation

Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB. Anticancer potential of silymarin: from bench to bed side. Anticancer Res. 2006 Nov-Dec;26(6B):4457-98. — View Citation

Alcaide J, Funez R, Rueda A, Perez-Ruiz E, Pereda T, Rodrigo I, Covenas R, Munoz M, Redondo M. The role and prognostic value of apoptosis in colorectal carcinoma. BMC Clin Pathol. 2013 Oct 10;13(1):24. doi: 10.1186/1472-6890-13-24. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Kim SH, Choo GS, Yoo ES, Woo JS, Han SH, Lee JH, Jung JY. Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells. Oncol Rep. 2019 Nov;42(5):1904-1914. doi: 10.3892/or.2019.7295. Epub 2019 Aug 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change between groups in response rate (RECIST)	Tumor response is characterized by both objective response rates (ORR=Complete response + partial response) and disease control rate (DCR= complete response + partial response + stable disease). In addition, complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) will be evaluated.; Follow-up for one year will be carried out to determine progression free survival (PFS) and the overall survival (OS) or one year survival.	At baseline, pre-intervention and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days)
Secondary	Changes in serum levels of the measured biological marker serum carcinoembryonic antigen in ng/ ml or Carbohydrate antigen 19-9 in U/ml.	As Tumor Marker if the baseline is elevated.	3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).
Secondary	Changes in serum levels of the measured biological marker serum vascular endothelial growth factor in pg/ml.	As a marker of angiogenesis.	3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).
Secondary	Changes in serum levels of the measured biological marker serum Bax protein in ng/ml.	As a marker for apoptosis.	3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).
Secondary	Changes in serum levels of the measured biological marker serum permeability glycoprotein in ng/ml	As a marker for chemo-sensitization.	3 Months. At baseline( pre-intervention )and at the end of last chemotherapy cycle ( 3 months from the beginning ) patients will recieve either Folfiri 6 cycles ( each cycle is 14 days) or Xeliri 4 cycles ( each cycle is 21 days).