Upper GI CancerPhase 2/3NCT01829178
Evaluation of Effects of Silymarin on Cisplatin Induced Nephrotoxicity in Upper Gastrointestinal Adenocarcinoma
A Phase 2/3 study testing Silymarin and chemotherapy in people with Upper GI Cancer and Cisplatin Adverse Reaction, run by Tehran University of Medical Sciences at 1 site in Iran.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Upper GI Cancer, Cisplatin Adverse Reaction
- What is being tested?
- Silymarin and chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteIran
- Study dates
- Aug 2013to Sep 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 )
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity
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.
Read the 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
- Being tested
- Silymarin, Placebo, chemotherapy
- Keywords
- cisplatin, nephrotoxicity, antioxidant, urine neutrophil gelatinase-associated lipocalin (NGAL)
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SilymarinDrug
Also called Milk thistle
Silymarin 420 mg in 3 divided dose plus standard chemotherapy
PlaceboDrug
Also called Identical inert tablet to mimic silymarin (140 mg)
placebo tablets: 420 mg in 3 divided dose
chemotherapyDrug
Also called Cisplatin, fluorouracil, Docetaxel
All patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| 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] Receives: 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 Receives: Drug: Silymarin; Drug: chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 9 weeks
Secondary outcomes (2)
Changes in VEGF Serum concentration
To assess interaction between silymarin and cancer chemotherapy serum vascular endothelial growth factor will be measured.
Measured: up to 9 weeks
Tissue activity of caspase 3
To assess interaction between silymarin and cancer chemotherapy Tissue activity of caspase 3will be measured.
Measured: up to 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2013 (estimated)
- Study startAug 2013
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Upper GI CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tehran University of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Simin Dashti-Khavidaki, Dr, Study chair, Tehran University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01829178
- Sponsor's protocol ID
- 91-03-33-18878
- Status last verified
- May 2015
- First submitted
- 11 Jan 2013
- Last updated
- 13 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity
- ClinicalTrials.gov ID
- NCT01829178
- Acronym / sponsor ID
- 91-03-33-18878
- Conditions
- Upper GI Cancer, Cisplatin Adverse Reaction
- Keywords
- cisplatin, nephrotoxicity, antioxidant, urine neutrophil gelatinase-associated lipocalin (NGAL)
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Tehran University of Medical SciencesUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 11 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control arm | Placebo comparator | Drug: Placebo, Drug: chemotherapyPlacebo 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] |
| Exprimental: Silymarin and chemotherapy | Active comparator | Drug: Silymarin, Drug: chemotherapysilymarin 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- age>18 years
- diagnosed
- measurable upper gastrointestinal adenocarcinoma
- swallow problem
- would like to participate in the study
Key exclusion criteria (12 listed)
- end stage renal disease
- requiring dialysis
- post transplantation
- receiving contrast media during last 72 hours
- chronic use of corticosteroids
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SilymarinAlso: Milk thistleSilymarin 420 mg in 3 divided dose plus standard chemotherapy | Drug | Exprimental: Silymarin and chemotherapy |
| PlaceboAlso: Identical inert tablet to mimic silymarin (140 mg)placebo tablets: 420 mg in 3 divided dose | Drug | Control arm |
| chemotherapyAlso: Cisplatin, fluorouracil, DocetaxelAll patients will receive standard chemotherapy: cisplatin 50-60mg/m2 + fluorouracil 750 mg/m2 + docetaxel 60-80 mg/m2 | Drug | Control arm, Exprimental: Silymarin and chemotherapy |
Primary outcome
Urine concentration of NGAL
Time frame: up to 9 weeks
All subject receive silymarin at dose of 420mg or placebo in three dose for 65 consecutive day, urine NGAL concentration will be measured.
2 secondary outcomes
Changes in VEGF Serum concentration
Time frame: up to 9 weeks
Tissue activity of caspase 3
Time frame: up to 9 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simin Dashti-Khavidaki, Dr study chair
Tehran University of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Silymarin and chemotherapy in people with Upper GI Cancer and Cisplatin Adverse Reaction, run by Tehran University of Medical Sciences at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urine concentration of NGAL (time frame: up to 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2015.