Contact information
Type
Scientific
Primary contact
Dr M van Essen
ORCID ID
Contact details
Erasmus Medical Centre
Dr Molewaterplein 40
Rotterdam
3015 GD
Netherlands
+31 (0)10 463 5963
d.j.kwekkeboom@erasmusmc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
Chemosensitisation with capecitabine improves the percentage of patients with objective tumour responses who are also treated with [177Lu-DOTA0,Tyr3]octreotate.
Ethics approval
Ethics approval received from the local medical ethics committee
Study design
Randomised, active controlled, parallel group, multicentre trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Neuroendocrine gastro-entero-pancreatic tumours
Intervention
Arm one: Treatment with the radioactive somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate
Arm two: Treatment with [177Lu-DOTA0,Tyr3]octreotate and capecitabine
Intervention type
Drug
Phase
Not Specified
Drug names
[177Lu-DOTA0,Tyr3]octreotate
Primary outcome measure
Efficacy and safety assessments:
Objective response as determined by SWOG criteria is the main efficacy endpoint. Upon entry, subjects must have at least one measurable site of disease based on the SWOG response criteria. All lesions must be identified at baseline by physical exam, CT or Magnetic Resonance Imaging (MRI) within two months prior to the start of treatment. Changes from baseline will be assessed six weeks after the last treatment, and three, six, and 12 months after the last treatment, and then every six months, until progression occurs. Patients who discontinue early due to clinical disease progression (unsatisfactory therapeutic effect) do not require a tumour assessment.
The overall survival of patients treated with radio-labelled somatostatin analogue will be calculated from the first day of treatment until the day of death. In patients who change to other anti-tumour treatments or who are lost to follow-up censored survival will be determined by the last regular visit. The time to progression is calculated from the first day of treatment to the day of documented progression.
Tumour Assessment/SWOG:
For CT imaging at entry, a triphasic, contrast enhanced study should be performed with a slice distance of 5 or 8 mm, and continuous slices. For follow-up CT imaging, triphasic imaging is not mandatory: the imaging phase at which the lesions are best recognised can be repeated instead.
Tumour response will be recorded according to the SWOG criteria by the investigators. Bidimensional tumour measurements from CT or MRI scans that were performed before treatment enrolment and after completing the therapy will be recorded.
End of Study:
The completion of the last day of the last study period or the date and reasons of premature discontinuation from the study will be recorded. End-point of the follow-up period is disease progression or death. The follow-up may be ended five years after the conclusion of treatment. However, in all patients the collection of toxicity data (haematology, renal function) should be continued either by the investigator, referring physician, or general practitioner.
Survival Information:
Information regarding the status of the patient, date of last contact or date of death will be collected.
Secondary outcome measures
1. Changes in serum chromogranin-A concentrations
2. Safety of treatment as measured by the rate of adverse events and the monitoring of selected laboratory evaluations
3. Effect of the different treatment arms on Quality of Life as measured by the EORTC QLQ-C30 questionnaire
4. Effects on Tumour Growth Rate (TGR)
Overall trial start date
01/03/2007
Overall trial end date
01/03/2010
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Presence of histology proven Gastro-Entero-Pancreatic (GEP) tumour(s), including bronchial carcinoids
2. Presence of somatostatin-receptors on the known tumour lesions demonstrated by OctreoScan® within six months of the first dose of radio-labelled octreotate/octreotide. The uptake on the OctreoScan® should be at least as high as normal liver uptake on planar imaging
3. Life expectancy greater than 12 weeks
4. Serum creatinine less than than 150 µmol/litre or 1.7 mg/dL, and a measured creatinine clearance (or measured Glomerular Filtration Rate [GFR] using plasma clearance methods, not gamma-camera based) of greater than or equal to 50 mL/min
5. Haemoglobin (Hgb) concentration greater than or equal to 5.5 mmol/L (greater than or equal to 8.9 g/dL); White Blood Cells (WBC) greater than or equal to 2 x 10^9/L (2000/mm^3); platelets greater than or equal to 100 x 10^9/L (100 x 10^3/mm^3)
6. Total bilirubin less than 3 x Upper Limit of Normal (ULN)
7. Serum albumin less than 30 g/L, or serum albumin greater than or equal to 30 g/L but normal prothrombin time
8. Karnofsky Performance Status greater than or equal to 60
9. Presence of at least one measurable site of disease
10. Patient’s written voluntary informed consent to participate in the study, obtained prior to enrolment into the study. The informed consent must be maintained in the investigator's study files
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
200
Participant exclusion criteria
1. Possible surgery with curative intent
2. Surgery, radiotherapy, chemotherapy, or other investigational therapy within three months of the start of therapy
3. Patients with known brain metastases unless these metastases have been treated and stabilised for at least six months prior to study start. Patients with a history of brain metastases must have a head Computed Tomography (CT) with contrast to document stable disease prior to study start
4. Uncontrolled congestive heart failure
5. Any subject who is taking concomitant medications which decrease renal function (such as aminoglycoside antibiotics)
6. Any subject receiving therapy with somatostatin analogues, unless the dose has been stable for at least three months prior to the first cycle in this study and the disease status during these three months has been documented by South West Oncology Group (SWOG) criteria as described in this study
7. Any subject receiving therapy with short-acting somatostatin analogues in whom these analogues cannot be interrupted for 12 hours before and 12 hours after the administration of the radio-labelled somatostatin analogues, or any subject receiving therapy with long-acting somatostatin analogues in whom these analogues cannot be interrupted for at least six weeks before the administration of the radio-labelled somatostatin analogues, unless the uptake on the OctreoScan® during continued somatostatin analogue medication is at least as high as normal liver uptake on planar imaging
8. In patients with unusual haematological parameters, including an increased Mean red Cell Volume (MCV) (greater than 105 fL), and especially in those who had previous chemotherapy, the advice of a haematologist should be sought, for adequate further work-up
9. Subjects with another significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with completion of the study
10. Pregnancy
11. Prior radiation therapy to more than 25% of the bone marrow
Recruitment start date
01/03/2007
Recruitment end date
01/03/2010
Locations
Countries of recruitment
Netherlands
Trial participating centre
Erasmus Medical Centre
Rotterdam
3015 GD
Netherlands
Sponsor information
Organisation
Erasmus Medical Centre (The Netherlands)
Sponsor details
Department of Nuclear Medicine
Rotterdam
3015 GJ
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
Erasmus Medical Centre (The Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list