A multicentre study comparing treatment of patients with neuroendocrine gastro-entero-pancreatic tumours with 177Lu-octreotate versus combined 177Lu-octreotate and capecitabine treatment

ISRCTN	ISRCTN30356763
DOI	https://doi.org/10.1186/ISRCTN30356763
Protocol serial number	NL889 (NTR913)
Sponsor	Erasmus Medical Centre (The Netherlands)
Funder	Erasmus Medical Centre (The Netherlands)

Submission date: 07/03/2007
Registration date: 07/03/2007
Last edited: 26/08/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr M van Essen
Scientific

Erasmus Medical Centre
Dr Molewaterplein 40
Rotterdam
3015 GD
Netherlands

Phone	+31 (0)10 463 5963
Email	d.j.kwekkeboom@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Randomised, active controlled, parallel group, multicentre trial
Secondary study design	Randomised controlled trial
Scientific title	A multicentre study comparing treatment of patients with neuroendocrine gastro-entero-pancreatic tumours with 177Lu-octreotate versus combined 177Lu-octreotate and capecitabine treatment
Study objectives	Chemosensitisation with capecitabine improves the percentage of patients with objective tumour responses who are also treated with [177Lu-DOTA0,Tyr3]octreotate.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	[177Lu-DOTA0,Tyr3]octreotate
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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)
Completion date	01/03/2010

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target sample size at registration	200
Key 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
Key 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
Date of first enrolment	01/03/2007
Date of final enrolment	01/03/2010

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus Medical Centre

Rotterdam
3015 GD
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

26/08/2021: Proactive update review. No publications found. Search options exhausted.