Effect of Silymarin in Metastatic Colorectal Cancer Patients

NCT05631041 | Unknown Phase 3

• 1 other identifier: Silymarin in Colorectal Cancer
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Changes in serum levels of the measured biological marker serum carcinoembryonic antigen in ng/ ml or Carbohydrate antigen 19-9 in U/ml.

  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).

• Changes in serum levels of the measured biological marker serum vascular endothelial growth factor in pg/ml.

  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).

• Changes in serum levels of the measured biological marker serum Bax protein in ng/ml.

  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).

• Changes in serum levels of the measured biological marker serum permeability glycoprotein in ng/ml

  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).

Study Arms (2)

Control group

NO INTERVENTION

Group I (Control group ; n=32) which will receive FOLFIRI regimen (5-flourouracil, leucovorin, irinotecan) or XELIRI (Capecitabine and irinotecan) with or without target therapy (Bevacizumab).

Silymarin group

ACTIVE COMPARATOR

Group II: (Silymarin group ; n=32) which will receive FOLFIRI regimen (5-flourouracil, leucovorin, irinotecan) or XELIRI (Capecitabine and irinotecan) with or without target therapy (Bevacizumab). plus silymarin 140 mg once daily.

Drug: Silymarin

Interventions

Silymarin DRUG

participants in silymarin group will receive silymarin 140 mg once daily.

Silymarin group

Eligibility Criteria

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

You may qualify if:

• \- 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).

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• Tanta University: lead

Study Sites (1)

faculty of Pharmacy , Tanta University

Tanta, Egypt

RECRUITING

Related Publications (5)

• 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.

  PMID: 30207593 BACKGROUND

• 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.

  PMID: 12352245 BACKGROUND

• 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.

  PMID: 17201169 BACKGROUND

• 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.

  PMID: 31485597 BACKGROUND

• 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.

  PMID: 24106912 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Silymarin

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)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• shimaa yassin, pharmacist

  Tanta University

  PRINCIPAL INVESTIGATOR

• Tarek Mostafa, professor

  Tanta University

  STUDY DIRECTOR

• Sahar Elhaggar, professor

  Tanta University

  STUDY DIRECTOR

• Mohammed Alam El-Din, professor

  Tanta University

  STUDY DIRECTOR

Central Study Contacts

Shimaa Yassin, pharmacist

CONTACT

01003228294; shaimaa150849@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: principal Investigator

Study Record Dates

• First Submitted: November 8, 2022
• First Posted: November 30, 2022
• Study Start: December 31, 2022
• Primary Completion: November 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 22, 2023

Record last verified: 2023-12

Locations

EG (1)