Pharmacokinetic study of capecitabine after total gastrectomy for stomach adenocarcinoma

ISRCTN	ISRCTN15898585
DOI	https://doi.org/10.1186/ISRCTN15898585
ClinicalTrials.gov number	NCT00871273
Secondary identifying numbers	CAP002

Submission date: 15/06/2009
Registration date: 28/08/2009
Last edited: 14/05/2019

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

http://cancerhelp.cancerresearchuk.org/trials/a-study-capecitabine-works-stomach-cancer-stomach-removed

Contact information

Prof Duncan Jodrell
Scientific

Oncology Centre
Box 193
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Study information

Study design	Multicentre non-randomised single-arm open-label study
Primary study design	Interventional
Secondary study design	Non randomised study
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A pharmacokinetic study of capecitabine in patients undergoing peri-operative chemotherapy and a total gastrectomy for adenocarcinoma of the stomach
Study acronym	CAP002
Study hypothesis	To establish the pharmacokinetics (PK) of capecitabine in patients who have undergone a total gastrectomy, i.e. the action of drug capecitabine in the body over a period of time, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion.
Ethics approval(s)	Sunderland Research Ethics Committee, 16/06/2009, ref: 09/H0904/38
Condition	Gastric adenocarcinoma
Intervention	This is a clinical trial to evaluate the PK of adjuvant capecitabine in patients who have undergone a total gastrectomy. The study will compare the pharmacokinetic profile of capecitabine administered to patients with gastric cancer pre- and post-gastrectomy (using patients as their own controls) and also compare the data accrued with historical data for capecitabine PK. The aim is to ensure equivalent capecitabine exposure following total gastrectomy. Screening tests will consist of demographic details, complete medical history, physical exam, vital signs, haematology and biochemistry tests. Electrocardiogram (ECG), tumour measurement (computed tomography [CT] abdomen, chest X-ray or CT chest) and a serum or urine pregnancy test (for women of childbearing potential) will also be performed. Haematology and biochemistry will be repeated prior to each study drug administration. All patients will receive ECX chemotherapy which includes epirubicin 50 mg/m^2 (intravenous [iv] bolus) on day 1, cisplatin 60 mg/m^2 (iv infusion) on day 1 and oral capecitabine chemotherapy at a dose of 625 mg/m^2 administered twice daily at 12 hourly intervals for 21 consecutive days out of a 21-day cycle. Capecitabine and its metabolites (DFCR, DFUR and 5-FU) plasma levels will be measured during cycles 1 and 4 in all patients, using a validated HPLC-MS method. An optional pharmacogenetic sample will be collected prior to the start of chemotherapy treatment. Treatment will continue for 3 cycles pre-operatively and 3 cycles post-operatively unless there is evidence of disease progression on chemotherapy, unacceptable toxicity or treatment is discontinued at the patient's request.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Capecitabine
Primary outcome measure	To establish the PK of capecitabine in patients who have undergone a total gastrectomy, measured at week 18 +/- 2
Secondary outcome measures	1. To compare the PK profile of capecitabine administered to patients with gastric cancer pre- and post-gastrectomy and to compare this to historical data of capecitabine PK values in patients with other cancer types 2. To ensure equivalent capecitabine exposure when compared to previous studies using patients who have not undergone such surgery Measured at PK analysis.
Overall study start date	01/08/2009
Overall study end date	30/11/2013
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	12
Participant inclusion criteria	1. Histological confirmation of gastric carcinoma suitable for potentially curative resection 2. Surgery must be planned to involve a total gastrectomy 3. No concurrent mechanical or malabsorptive disorders precluding affective oral administration of the drug (excluding early satiety related to the presence of the malignancy) 4. Aged greater than or equal to 18 years, either sex 5. World Health Organisation (WHO) performance status of less than or equal to 2 6. Haematological and biochemical indices (these measurements must be performed within one week prior to the patient going on study): 6.1. Haemoglobin (Hb) greater than or equal to 9.0 g/dl 6.2. Neutrophils greater than or equal to 1.5 x 10^9/l 6.3. Platelets (Plts) greater than or equal to 100 x 10^9/l 6.4. Serum bilirubin less than or equal to 1.5 x upper normal limit (ULN) 6.5. Alanine amino-transferase (ALT) and/or aspartate amino-transferase (AST) less than or equal to 2.0 x ULN (if both are measured, both must be less than or equal to 2.0 x ULN) 6.6. Calculated creatinine clearance greater than or equal to 50 ml/min (uncorrected value) or isotope clearance measurement greater than or equal to 50 ml/min 7. Female patients of child-bearing potential must have a negative serum or urine pregnancy test within two weeks prior to enrolment and agree to use appropriate medically approved contraception for four weeks prior to entering the trial, during the trial, and for six months afterwards 8. Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards 9. Written, informed consent provided 10. Ability of the patient to co-operate with treatment and follow up must be ensured 11. Patients receiving oral anti-coagulation prior to entry into the study, must be converted to low molecular weight heparin in light of the interaction between capecitabine and warfarin
Participant exclusion criteria	1. Patients with gastric lymphoma or other histological diagnosis 2. Any evidence of malignant ascites, peritoneal or liver metastasis, spread to other distant abdominal or extra-abdominal organs 3. History of confirmed ischaemic heart disease, concurrent congestive heart failure or prior history of class III/IV cardiac disease 4. Concurrent mechanical or malabsorptive disorders precluding effective oral administration of the drug 5. Use of other concomitant chemotherapy 6. Pregnancy or lactation 7. Patients known to be serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV) 8. Patients who are high medical risks because of non-malignant systemic disease including active uncontrolled infection 9. Any other serious medical or psychological condition precluding adjuvant treatment 10. Patients with any other condition that in the Investigator's opinion would not make the patient a good candidate for the clinical trial
Recruitment start date	01/11/2009
Recruitment end date	30/11/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Oncology Centre

Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre

R&D Department, Box 146
Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Website	http://www.cuh.org.uk/addenbrookes/addenbrookes_index.html
"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Industry

Roche (UK)
Government organisation / For-profit companies (industry)

Alternative name(s): F. Hoffmann-La Roche Ltd, F. Hoffmann-La Roche & Co, F. Hoffmann-La Roche AG, Roche Holding AG, Roche Holding Ltd, Roche Holding, Roche Holding A.G., Roche Holding, Limited, F. Hoffmann-La Roche & Co.
Location: Switzerland

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No

Editorial Notes

14/05/2019: ClinicalTrials.gov states that this trial was terminated due to slow recruitment, change to clinical environment reducing the pool of potentially eligible patients, and availability of data from another similar study.
11/12/2017: No publications found, verifying study status with principal investigator.