A multicenter study comparing treatment of patients with neuroendocrine Gastro-Entero-Pancreatic (GEP) tumors with 177Lu-octreotate versus combined 177Lu-octreotate and capecitabine treatment.

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR913
• Date of registration: 19/02/2007
• Primary sponsor: Erasmus Medical Center, Department of Nucleair Medicine
• Public title: A multicenter study comparing treatment of patients with neuroendocrine Gastro-Entero-Pancreatic (GEP) tumors with 177Lu-octreotate versus combined 177Lu-octreotate and capecitabine treatment.
• Scientific title: A multicenter study comparing treatment of patients with neuroendocrine Gastro-Entero-Pancreatic (GEP) tumors with 177Lu-octreotate versus combined 177Lu-octreotate and capecitabine treatment. - N/A
• Date of first enrolment: 1/3/2007
• Target sample size: 200
• Recruitment status: pending
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=913
• Study type: intervention
• Study design: Randomised: Yes; Masking: None; Control: Active; Group: Parallel; Type: -

Countries of recruitment

The Netherlands

Contacts

• Name: D.J. Kwekkeboom

• Name: M. Essen, van

Key inclusion & exclusion criteria

Inclusion criteria: Inclusion criteria
1. Presence of histology proven GEP tumor(s), including bronchial carcinoids;
2. Presence of somatostatin-receptors on the known tumor lesions demonstrated by OctreoScan® within 6 months of the first dose of radiolabelled 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 £150 µmol/liter or 1.7 mg/dL, and a measured creatinine clearance (or measured GFR using plasma clearance methods, not gamma-camera based) of ³50 mL/min;
5. Hemoglobin (Hgb) concentration ³5.5 mmol/L (³8.9 g/dL); WBC ³ 2*109/L (2000/mm3); platelets ³ 100*109/L (100*103/mm3);
6. Total bilirubin £3 x ULN;
7. Serum albumin > 30 g/L, or serum albumin £ 30 g/L but normal prothrombin time;
8. Karnofsky Performance Status ³ 60;
9. Presence of at least 1 measurable site of disease;
10. Patient?s written voluntary informed consent to participate in the study, obtained prior to enrollment into the study. The informed consent must be maintained in the investigator's study files.

Exclusion criteria: 1. Possible surgery with curative intent;
2. Surgery, radiotherapy, chemotherapy, or other investigational therapy within 3 months of the start of therapy;
3. Patients with known brain metastases unless these metastases have been treated and stabilized for at least six months prior to study start. Patients with a history of brain metastases must have a head 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 3 months prior to the first cycle in this study and the disease status during these 3 months has been documented by 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 radiolabelled somatostatin analogues, or any subject receiving therapy with long-acting somatostatin analogues in whom these analogues cannot be interrupted for at least 6 weeks before the administration of the radiolabelled 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 hematological parameters, including an increased MCV (>105 fL), and especially in those who had previous chemotherapy, the advice of a hematologist should be seeked, 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.


Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Lutetium-octreotate , Neuroendocrine tumors, Somatostatin analogues , Lutetium-177 , Chemosensitization

Intervention(s)

Treatment with the radioactive somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate (arm 1)
Treatment with [177Lu-DOTA0,Tyr3]octreotate and capecitabine (arm 2)

Primary Outcome(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 MRI within 2 months prior to the start of treatment. Changes from baseline will be assessed 6 weeks after the last treatment, and 3, 6, and 12 months after the last treatment, and then every 6 months, until progression occurs. Patients who discontinue early due to clinical disease progression (unsatisfactory therapeutic effect) do not require a tumor assessment.

The overall survival of patients treated with radiolabelled somatostatin analogue will be calculated from the first day of treatment until the day of death. In patients who change to other anti-tumor 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.

Tumor 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 recognized can be repeated instead.

Tumor response will be recorded according to the SWOG criteria by the investigators. Bidimensional tumor measurements from CT or MRI scans that were performed before treatment enrollment 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 5 years after the conclusion of treatment. However, in all patients the collection of toxicity data (hematology, 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(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 tumor growth rate (TGR).

Secondary ID(s)

ISRCTN30356763

N/A

Source(s) of Monetary Support

Erasmus Medical Center, Department of Nucleair Medicine