Neoplasms, ColorectalPhase 1NCT00920803
A Clinical Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SRT501 in Subjects With Colorectal Cancer and Hepatic Metastases
A Phase 1 study testing SRT501 in people with Neoplasms, Colorectal, run by Sirtris, a GSK Company at 1 site in United Kingdom.
Trial summary
The primary purpose of this study is to determine the safety and tolerability of SRT501 (5.0 g) in subjects with colorectal cancer and hepatic metastases when administered once daily for 14 days. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Colorectal
- What is being tested?
- SRT501
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 19 Aug 2008to 11 Nov 2009
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be male or female greater than 18 years of age.
- Have histologically or cytologically confirmed and diagnosed colorectal cancer with hepatic metastases.
- Have not received chemotherapy or anti-neoplastic therapy for a malignancy within six weeks of first dose of SRT501 or placebo.
- Have a life expectancy of greater than 3 months.
- Voluntarily sign an Ethics Committee (EC)-approved informed consent form (ICF) to participate in the study after all relevant aspects of the study have been explained and discussed with the subject.
- Be deemed, in the Investigator's opinion, to be able to physically comply with SRT501 dosing.
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- Be amenable to surgical resection of the hepatic metastases.
- Be clear of any history of HIV 1 and 2 and hepatitis B and C.
- Have a normal 12-lead ECG or an ECG with abnormality considered to be clinically insignificant.
- Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
- Female subject is either post-menopausal, surgically sterilized or be a woman of child bearing potential (WCBP) who has documented use of clinically prescribed hormonal contraceptives use consistently for three months prior to study entry. Females of child bearing potential, as well as their partners, must also use appropriate double-barrier birth control while participating in the study and for 28 days following the last dose of study drug. If a woman of child bearing potential has a surgically sterile partner, then that female is permitted to enroll if double-barrier birth control is practiced.
Who cannot join
- Subject has a history / evidence of allergy or hypersensitivity to resveratrol.
- Subject has had a major illness (other than colorectal cancer) in the past three months or any significant ongoing chronic medical illness that the Investigator would deem unfavorable for enrollment.
- Subject has inadequate organ function at the Screening visit as defined by the following laboratory values:
- Platelet count ≤100,000 x 10^9/L
- Hemoglobin ≤10.0 g/dL
- Subjects with lower hemoglobin may be included at the Investigator's discretion if the cause of anemia is due to bleeding from their tumor and post transfusion hemoglobin ≥10g/dL prior to dosing.
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- Absolute neutrophil count (ANC) ≤1500 x 10^6/L
- Aspartate transaminase (AST) ≥2.5 x the upper limit of the normal range (ULN)
- Alanine transaminase (ALT) ≥2.5 x ULN
- Creatinine ≥ 140 umol/L
- Albumin ≤3 g/dL
- Subject has a history of or current gastro-intestinal diseases influencing drug absorption, with the exception of an appendectomy and/or colorectal cancer.
- Subject has liver impairment as indicated by total bilirubin ≥2 x ULN, unless clearly related to the disease (ie, biliary occlusion due to tumor compression or confirmed Gilbert's Disease as documented by the Investigator).
- Subject had a myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- Excessive alcohol intake (more than UK recommended limit - 28 or 21 units per week for men or women respectively).
- Subject has uncontrolled brain metastases or central nervous system disease.
- Subject has participated in a clinical trial within the past three months.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-hCG pregnancy test result obtained during the Screening period. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
GSK Investigational Site
Leicester, Leicestershire, LE1 5WW
About this study
Official title: A Phase 1, Double-Blind, Randomized Clinical Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SRT501 in Subjects With Colorectal Cancer and Hepatic Metastases
The primary purpose of this study is to determine the safety and tolerability of SRT501 (5.0 g) in subjects with colorectal cancer and hepatic metastases when administered once daily for 14 days.
The purpose is to also characterize the pharmacokinetic profile of SRT501 (5.0 g) by assessing levels of SRT501 and metabolites in blood, urine, bile and normal and malignant metastatic tissues in subjects with colorectal cancer and hepatic metastases when administered once daily for 14 days.
The secondary purpose is to examine the pharmacodynamics of SRT501 activity in both normal and malignant tissue samples, including blood and/or bodily fluids.
Read the detailed description
This is a randomized, double-blind, placebo-controlled, inpatient/outpatient study to assess the safety, pharmacokinetics, and pharmacodynamics of SRT501 in subjects diagnosed with colorectal cancer and hepatic metastases. Fifteen subjects aged 18 years of age and older who fulfill the inclusion/exclusion criteria, will be enrolled in this study. Ten subjects, if eligible, will be randomized to receive SRT501 and 5 subjects, if eligible, will be randomized to receive placebo. Subjects will sign the informed consent form prior to any study-related procedures. If eligible, subjects will consent to receive 5.0 g of SRT501 or placebo, to be administered once daily as an oral reconstituted powder, for 14 days at the same time each day. On Days 1 and 2, SRT501 or placebo will be administered approximately 15-30 minutes following the consumption of a standardized breakfast to allow for PK sample collection. On all other days, SRT501 or placebo will be administered approximately 15-30 minutes following the consumption of the evening meal. Following the course of SRT501 or placebo administration, subjects will undergo scheduled surgical removal of their metastatic liver disease as well as non-diseased tissue and these samples will be evaluated for SRT501 concentrations and pharmacodynamic markers of neoplastic activity (such as cell differentiation, apoptosis, proliferation, etc.). Due to scheduling and surgical availability, subjects can receive SRT501 or placebo for a minimum of 10 days and a maximum of 21 days. If diseased colon tissue is also scheduled to be removed during resection, both diseased and normal colon tissue will also be collected for analysis. Participants will be required to return to the study center on Day 2 for a 24-hour PK sample and the evening prior to their scheduled surgical resection as well as per the Institution's standards of care for recovery following the surgical procedure.
- Conditions
- Neoplasms, Colorectal
- Being tested
- Placebo, SRT501
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo will be supplied in clinical kits as a powder which will be reconstituted with vehicle and water into a liquid suspension. Placebo must be used immediately following mixing. Placebo will be administered orally, once daily for 14 days.
SRT501Drug
SRT501 will be supplied in clinical kits as a powder which will be reconstituted with vehicle and water into a liquid suspension. The final drug product must be used immediately following mixing. SRT501 will be administered orally, once daily for 14 days.
| Study group | Role | What they receive |
|---|---|---|
| 5g SRT501 | Active comparator | 5.0 g of SRT501 will be administered once daily as an oral reconstituted powder, for 14 days at the same time each day. On Days 1 and 2, SRT501 will be administered approximately 15-30 minutes following the consumption of a standardized breakfast. On all other days, SRT501 will be administered approximately 15-30 minutes following the consumption of the evening meal. Following the course of SRT501 administration, subjects will undergo scheduled surgical removal of their metastatic liver disease as well as non-diseased tissue. Due to scheduling and surgical availability, subjects can receive SRT501 for a minimum of 10 days and a maximum of 21 days. Receives: Drug: SRT501 |
| Placebo | Placebo comparator | Placebo will be administered once daily as an oral reconstituted powder, for 14 days at the same time each day. On Days 1 and 2, placebo will be administered approximately 15-30 minutes following the consumption of a standardized breakfast to allow for PK sample collection. On all other days, placebo will be administered approximately 15-30 minutes following the consumption of the evening meal. Following the course of placebo administration, subjects will undergo scheduled surgical removal of their metastatic liver disease as well as non-diseased tissue. Due to scheduling and surgical availability, subjects can receive placebo for a minimum of 10 days and a maximum of 21 days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of SRT501 when administered once daily for 14 days.
Measured: Safety will be continually assessed while subjects are on study.
To characterize the pharmacokinetic profile of SRT501 in blood and normal and malignant metastatic tissues when administered once daily for 14 days.
Measured: Pharmacokinetic samples will be obtained on Days 1, 2, 14, and 15.
Secondary outcomes (1)
To examine the pharmacodynamics of SRT501 activity in both normal and malignant tissue samples and blood.
Measured: Pharmacodynamic samples will be collected on Days 14 and 15 and will be analyzed at the end of the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2009 (estimated)
- Study start19 Aug 2008
- Primary completion11 Nov 2009
- Study completion11 Nov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, ColorectalStudies 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sirtris, a GSK Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00920803
- Sponsor's protocol ID
- 113221
- Status last verified
- Jun 2017
- First submitted
- 12 Jun 2009
- Last updated
- 14 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, Brown K, Steward WP, Gescher AJ. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases--safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res (Phila). 2011 Sep;4(9):1419-25. doi: 10.1158/1940-6207.CAPR-11-0148. Epub 2011 Jun 16.
PubMed 21680702
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Double-Blind, Randomized Clinical Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of SRT501 in Subjects With Colorectal Cancer and Hepatic Metastases
- ClinicalTrials.gov ID
- NCT00920803
- Acronym / sponsor ID
- 113221
- Conditions
- Neoplasms, Colorectal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Sirtris, a GSK CompanyIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 19 Aug 2008 (actual)
- Primary completion
- 11 Nov 2009 (actual)
- Study completion
- 11 Nov 2009 (actual)
- First posted
- 15 Jun 2009 (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.
The primary purpose of this study is to determine the safety and tolerability of SRT501 (5.0 g) in subjects with colorectal cancer and hepatic metastases when administered once daily for 14 days.
The purpose is to also characterize the pharmacokinetic profile of SRT501 (5.0 g) by assessing levels of SRT501 and metabolites in blood, urine, bile and normal and malignant metastatic tissues in subjects with colorectal cancer and hepatic metastases when administered once daily for 14 days.
The secondary purpose is to examine the pharmacodynamics of SRT501 activity in both normal and malignant tissue samples, including blood and/or bodily fluids.
Detailed description
This is a randomized, double-blind, placebo-controlled, inpatient/outpatient study to assess the safety, pharmacokinetics, and pharmacodynamics of SRT501 in subjects diagnosed with colorectal cancer and hepatic metastases. Fifteen subjects aged 18 years of age and older who fulfill the inclusion/exclusion criteria, will be enrolled in this study. Ten subjects, if eligible, will be randomized to receive SRT501 and 5 subjects, if eligible, will be randomized to receive placebo. Subjects will sign the informed consent form prior to any study-related procedures. If eligible, subjects will consent to receive 5.0 g of SRT501 or placebo, to be administered once daily as an oral reconstituted powder, for 14 days at the same time each day. On Days 1 and 2, SRT501 or placebo will be administered approximately 15-30 minutes following the consumption of a standardized breakfast to allow for PK sample collection. On all other days, SRT501 or placebo will be administered approximately 15-30 minutes following the consumption of the evening meal. Following the course of SRT501 or placebo administration, subjects will undergo scheduled surgical removal of their metastatic liver disease as well as non-diseased tissue and these samples will be evaluated for SRT501 concentrations and pharmacodynamic markers of neoplastic activity (such as cell differentiation, apoptosis, proliferation, etc.). Due to scheduling and surgical availability, subjects can receive SRT501 or placebo for a minimum of 10 days and a maximum of 21 days. If diseased colon tissue is also scheduled to be removed during resection, both diseased and normal colon tissue will also be collected for analysis. Participants will be required to return to the study center on Day 2 for a 24-hour PK sample and the evening prior to their scheduled surgical resection as well as per the Institution's standards of care for recovery following the surgical procedure.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5g SRT501 | Active comparator | Drug: SRT5015.0 g of SRT501 will be administered once daily as an oral reconstituted powder, for 14 days at the same time each day. On Days 1 and 2, SRT501 will be administered approximately 15-30 minutes following the consumption of a standardized breakfast. On all other days, SRT501 will be administered approximately 15-30 minutes following the consumption of the evening meal. Following the course of SRT501 administration, subjects will undergo scheduled surgical removal of their metastatic liver disease as well as non-diseased tissue. Due to scheduling and surgical availability, subjects can receive SRT501 for a minimum of 10 days and a maximum of 21 days. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo will be administered once daily as an oral reconstituted powder, for 14 days at the same time each day. On Days 1 and 2, placebo will be administered approximately 15-30 minutes following the consumption of a standardized breakfast to allow for PK sample collection. On all other days, placebo will be administered approximately 15-30 minutes following the consumption of the evening meal. Following the course of placebo administration, subjects will undergo scheduled surgical removal of their metastatic liver disease as well as non-diseased tissue. Due to scheduling and surgical availability, subjects can receive placebo for a minimum of 10 days and a maximum of 21 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Be male or female greater than 18 years of age.
- Have histologically or cytologically confirmed and diagnosed colorectal cancer with hepatic metastases.
- Have not received chemotherapy or anti-neoplastic therapy for a malignancy within six weeks of first dose of SRT501 or placebo.
- Have a life expectancy of greater than 3 months.
- Voluntarily sign an Ethics Committee (EC)-approved informed consent form (ICF) to participate in the study after all relevant aspects of the study have been explained and discussed with the subject.
Key exclusion criteria (18 listed)
- Subject has a history / evidence of allergy or hypersensitivity to resveratrol.
- Subject has had a major illness (other than colorectal cancer) in the past three months or any significant ongoing chronic medical illness that the Investigator would deem unfavorable for enrollment.
- Subject has inadequate organ function at the Screening visit as defined by the following laboratory values:
- Subject has a history of or current gastro-intestinal diseases influencing drug absorption, with the exception of an appendectomy and/or colorectal cancer.
- Subject has liver impairment as indicated by total bilirubin ≥2 x ULN, unless clearly related to the disease (ie, biliary occlusion due to tumor compression or confirmed Gilbert's Disease as documented by the Investigator).
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 |
|---|---|---|
| PlaceboPlacebo will be supplied in clinical kits as a powder which will be reconstituted with vehicle and water into a liquid suspension. Placebo must be used immediately following mixing. Placebo will be administered orally, once daily for 14 days. | Drug | Placebo |
| SRT501SRT501 will be supplied in clinical kits as a powder which will be reconstituted with vehicle and water into a liquid suspension. The final drug product must be used immediately following mixing. SRT501 will be administered orally, once daily for 14 days. | Drug | 5g SRT501 |
Primary outcome
To determine the safety and tolerability of SRT501 when administered once daily for 14 days.
Time frame: Safety will be continually assessed while subjects are on study.
To characterize the pharmacokinetic profile of SRT501 in blood and normal and malignant metastatic tissues when administered once daily for 14 days.
Time frame: Pharmacokinetic samples will be obtained on Days 1, 2, 14, and 15.
1 secondary outcome
To examine the pharmacodynamics of SRT501 activity in both normal and malignant tissue samples and blood.
Time frame: Pharmacodynamic samples will be collected on Days 14 and 15 and will be analyzed at the end of the study.
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 14 Jun 2017.
- Background: PubMed 21680702Howells LM, Berry DP, Elliott PJ, Jacobson EW, Hoffmann E, Hegarty B, Brown K, Steward WP, Gescher AJ. Phase I randomized, double-blind pilot study of micronized resveratrol (SRT501) in patients with hepatic metastases--safety, pharmacokinetics, and pharmacodynamics. Cancer Prev Res (Phila). 2011 Sep;4(9):1419-25. doi: 10.1158/1940-6207.CAPR-11-0148. Epub 2011 Jun 16.
- Results for study 113221 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SRT501 in people with Neoplasms, Colorectal, run by Sirtris, a GSK Company at 1 site in United Kingdom.
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 11 inclusion and 18 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 14 Jun 2017. 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 United Kingdom. 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 phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
To determine the safety and tolerability of SRT501 when administered once daily for 14 days. (time frame: Safety will be continually assessed while subjects are on study.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00920803, which also lists 1 linked publication.
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 14 Jun 2017.