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

NCT ID: NCT01829178

Last Updated: 2015-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2014-09-30

Brief 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.

Detailed Description

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

Conditions

Upper GI Cancer; Cisplatin Adverse Reaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Control arm

Placebo 420 mg daily in three divided doses for 65 days as control along with \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2\]

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

placebo tablets: 420 mg in 3 divided dose

chemotherapy

Intervention Type: DRUG

All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2

Exprimental: Silymarin and chemotherapy

silymarin 420 mg daily in three divided doses for 65 days along with standard chemotherapy \[cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 +docetaxel 60-80 mg/m2 control

Group Type: ACTIVE_COMPARATOR

Silymarin

Intervention Type: DRUG

Silymarin 420 mg in 3 divided dose plus standard chemotherapy

chemotherapy

Intervention Type: DRUG

All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2

Interventions

Silymarin

Silymarin 420 mg in 3 divided dose plus standard chemotherapy

Intervention Type: DRUG

Placebo

placebo tablets: 420 mg in 3 divided dose

Intervention Type: DRUG

chemotherapy

All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2

Intervention Type: DRUG

Other Intervention Names

Milk thistle; Identical inert tablet to mimic silymarin (140 mg); Cisplatin; fluorouracil; Docetaxel

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tehran University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Simin Dashti-Khavidaki, Dr

Role: STUDY_CHAIR

Tehran University of Medical Sciences

Locations

Tehran University of Medical Science

Tehran, Tehran Province, Iran

Countries

Iran

Other Identifiers

91-03-33-18878

Identifier Type: -

Identifier Source: org_study_id