Effect of Silymarin in Metastatic Colorectal Cancer Patients

NCT ID: NCT05631041

Last Updated: 2023-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-12-31

Study Completion Date

2024-12-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type NO_INTERVENTION

No interventions assigned to this group

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.

Group Type ACTIVE_COMPARATOR

Silymarin

Intervention Type DRUG

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

Interventions

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Silymarin

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tanta University

OTHER

Sponsor Role lead

Responsible Party

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Shimaa Yassin Abdelghafaar Mohamed

principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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shimaa yassin, pharmacist

Role: PRINCIPAL_INVESTIGATOR

Tanta University

Tarek Mostafa, professor

Role: STUDY_DIRECTOR

Tanta University

Sahar Elhaggar, professor

Role: STUDY_DIRECTOR

Tanta University

Mohammed Alam El-Din, professor

Role: STUDY_DIRECTOR

Tanta University

Locations

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faculty of Pharmacy , Tanta University

Tanta, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Shimaa Yassin, pharmacist

Role: CONTACT

Phone: 01003228294

Email: [email protected]

Facility Contacts

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faculty of Pharmacy

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 30207593 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12352245 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17201169 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31485597 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24106912 (View on PubMed)

Other Identifiers

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Silymarin in Colorectal Cancer

Identifier Type: -

Identifier Source: org_study_id