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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

Phase 1
18 Years
Not Enrolling
Neoplasms, Colorectal, Colorectal Cancer

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Trial Information

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

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.

Inclusion Criteria:

- 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

- 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

- 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.

Exclusion Criteria:

- 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.

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Basic Science

Outcome Measure:

To determine the safety and tolerability of SRT501 when administered once daily for 14 days.

Outcome Time Frame:

Safety will be continually assessed while subjects are on study.

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

August 2008

Completion Date:

November 2009

Related Keywords:

  • Neoplasms, Colorectal
  • Colorectal Cancer
  • Neoplasms
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Liver Neoplasms