Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma

Cisplatin Adverse Reaction Clinical Trial

Official title:

Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01829178
• Other study ID #: 91-03-33-18878
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 11, 2013
• Last updated: May 11, 2015
• Start date: August 2013
• Est. completion date: September 2014

Study information

• Verified date: May 2015
• Source: Tehran University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ethics CommitteeIran: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Cisplatin is a potent chemotherapeutic agent that has been widely used to treat many solid tumours. acute renal failure, despite conservative fluid and electrolyte management, frequently reported adverse event and limiting cisplatin use. Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, anticancer and in animal model nephroprotective properties. Neutrophil gelatinase-associated lipocalin (NGAL) protein is a promising biomarker to detect acute kidney injury due to cisplatin. Milk thistle extract inhibitory effects on epidermal growth factor receptor, vascular endothelial growth factor and insulin-like growth factor-I have shown in the previous in-vitro studies.The aim of present study,a randomized double-blind placebo- controlled clinical trial, to investigate the therapeutic effect of silymarin on cisplatin induced nephrotoxicity and it's impact on chemotherapy. Fifty-eight patients with diagnosed upper gastrointestinal tract carcinomas randomized to silymarin (420mg) or placebo plus chemotherapy [cisplatin 50-60 mg/m2, 5-fluorouracil mg/m2, docetaxel 60-80 mg/m2 every 21 days] for 63 day after inclusion. serum creatinin, blood urea nitrogen (BUN), serum and urine electrolyte will be measured daily during chemotherapy.

changes in urine NGAL, serum vascular endothelial growth factor (VEGF)and caspase activity assessed up to 64 days.

Description:

This study will look for possible protective effects silymarin on kidney injury in patients receiving cisplatin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• age>18 years

• diagnosed

• measurable upper gastrointestinal adenocarcinoma

• swallow problem

• would like to participate in the study

• Glomerular filtration rate(GFR)>45ml/min/1.73m2

Exclusion Criteria:

• end stage renal disease

• requiring dialysis

• post transplantation

• receiving contrast media during last 72 hours

• chronic use of corticosteroids

• chronic use of angiotensin-converting enzyme inhibitor(ACEI )

• untreated hypo-and hyperthyroidism

• ejection fraction<60%

• active urinary tract infection

• iver disease ( five fold increase of liver enzyme in asymptomatic or 3 fold increase in symptomatic

• use of other nephrotoxic agents such as aminoglycoside, amphotericin

• karnofsky performance status <70

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cisplatin Adverse Reaction
• Upper GI Cancer

Intervention

Drug:
• Silymarin
Silymarin 420 mg in 3 divided dose plus standard chemotherapy
• Placebo
placebo tablets: 420 mg in 3 divided dose
• chemotherapy
All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2

Locations

Country	Name	City	State
Iran, Islamic Republic of	Tehran University of Medical Science	Tehran

Sponsors (1)

Lead Sponsor	Collaborator
Tehran University of Medical Sciences

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine concentration of NGAL	All subject receive silymarin at dose of 420mg or placebo in three dose for 65 consecutive day, urine NGAL concentration will be measured.	up to 9 weeks	Yes
Secondary	Changes in VEGF Serum concentration	To assess interaction between silymarin and cancer chemotherapy serum vascular endothelial growth factor will be measured.	up to 9 weeks	Yes
Secondary	Tissue activity of caspase 3	To assess interaction between silymarin and cancer chemotherapy Tissue activity of caspase 3will be measured.	up to 9 weeks	Yes