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

NCT01829178 | Completed Phase 2 DMC

• 1 other identifier: 91-03-33-18878
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Upper GI Cancer; Cisplatin Adverse Reaction

Keywords

cisplatin; nephrotoxicity; antioxidant; urine neutrophil gelatinase-associated lipocalin (NGAL)

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Changes in VEGF Serum concentration

  up to 9 weeks

• Tissue activity of caspase 3

  up to 9 weeks

Study Arms (2)

Control arm

PLACEBO COMPARATOR

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

Drug: Placebo; Drug: chemotherapy

Exprimental: Silymarin and chemotherapy

ACTIVE COMPARATOR

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

Drug: Silymarin; Drug: chemotherapy

Interventions

Silymarin DRUG

Silymarin 420 mg in 3 divided dose plus standard chemotherapy

Also known as: Milk thistle

Exprimental: Silymarin and chemotherapy

Placebo DRUG

placebo tablets: 420 mg in 3 divided dose

Also known as: Identical inert tablet to mimic silymarin (140 mg)

Control arm

chemotherapy DRUG

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

Also known as: Cisplatin, fluorouracil, Docetaxel

Control arm; Exprimental: Silymarin and chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tehran University of Medical Sciences: lead

Study Sites (1)

Tehran University of Medical Science

Tehran, Tehran Province, Iran

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Silymarin; milk-thistle extract; Drug Therapy; Cisplatin; Fluorouracil; Docetaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Simin Dashti-Khavidaki, Dr

  Tehran University of Medical Sciences

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2013
• First Posted: April 11, 2013
• Study Start: August 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: May 13, 2015

Record last verified: 2015-05

Locations

IR (1)