Effect of Silymarin in Metastatic Colorectal Cancer Patients

December 19, 2023 updated by: Shimaa Yassin Abdelghafaar Mohamed, Tanta University

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Egypt
      • Tanta, Egypt
        • Recruiting
        • faculty of Pharmacy , Tanta University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control group
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).
Active Comparator: Silymarin group
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
participants in silymarin group will receive silymarin 140 mg once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change between groups in response rate (RECIST)
Time Frame: 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)

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in serum levels of the measured biological marker serum carcinoembryonic antigen in ng/ ml or Carbohydrate antigen 19-9 in U/ml.
Time Frame: 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).
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).
Changes in serum levels of the measured biological marker serum vascular endothelial growth factor in pg/ml.
Time Frame: 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).
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).
Changes in serum levels of the measured biological marker serum Bax protein in ng/ml.
Time Frame: 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).
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).
Changes in serum levels of the measured biological marker serum permeability glycoprotein in ng/ml
Time Frame: 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).
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).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tanta University

Investigators

  • Principal Investigator: shimaa yassin, pharmacist, Tanta University
  • Study Director: Sahar Elhaggar, professor, Tanta University
  • Study Director: Mohammed Alam El-Din, professor, Tanta University
  • Study Director: Tarek Mostafa, professor, Tanta University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 31, 2022

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

November 8, 2022

First Submitted That Met QC Criteria

November 28, 2022

First Posted (Actual)

November 30, 2022

Study Record Updates

Last Update Posted (Actual)

December 22, 2023

Last Update Submitted That Met QC Criteria

December 19, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Silymarin in Colorectal Cancer

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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