Patients with inoperable, progressive, OctreoScan® positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours), who are treated with 20 mg or 30 mg Octreotide LAR at a fixed dose for at least 12 weeks prior to enrolment in the study. MedDRA version: 20.0 Level: LLT Classification code 10062392 Term: Carcinoid tumor of the small bowel System Organ Class: 10029104 - Neoplasms be
Conditions
Interventions
Trade Name: Lutathera 370 MBq/mL solution for infusion
Product Name: Lutathera 370 MBq/mL solution for infusion
Pharmaceutical Form: Solution for infusion
Sponsors
Advanced Accelerator Applications
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Presence of metastasized or locally advanced, inoperable (curative intent) at enrollment time, histologically proven, midgut carcinoid tumour (to be centrally confirmed). 2. Ki67 index = 20% (to be centrally confirmed). 3. Patients on Octreotide LAR at a fixed dose of 20 mg or 30 mg at 3-4 weeks intervals for at least 12 weeks prior to randomization in the study. 4. Patients =18 years of age. 5. Patients must have progressive disease based on RECIST Criteria, Version 1.1 (§Appendix 2) while receiving an uninterrupted fixed dose of Octreotide LAR (20-30 mg/3-4 weeks). Disease progression must be centrally confirmed. In order to make the assessment, two CT (or MRI) scans are required. The oldest scan must not be older than 3 years from the date of randomization. The most recent scan must not be older than 4 weeks from the date of randomization. Both scans must be obtained while the patient is receiving the same fixed dose of Octreotide LAR (20-30 mg/3-4 weeks) with the following exceptions; 1) it is acceptable if the oldest scan is obtained within 12 weeks of the patient receiving a fixed dose regimen of Octreotide LAR (20-30 mg/3-4 weeks); AND 2) it is acceptable for either scan to be obtained before or during the time a patient receiving a fixed dose of Octreotide LAR has switched to an equivalent dose of short acting Octreotide for up to 6 weeks in order to obtain an OctreoScan®, provided the patient returns to the Octreotide LAR fixed dose after the OctreoScan® has been obtained. 6. Confirmed presence of somatostatin receptors on all target lesions (for target/non-target/measurable lesions definition see §Appendix 2, Section 1 and 2, RECIST Criteria, Version 1.1) documented by CT/MRI scans, based on positive OctreoScan® imaging within 24 weeks prior to randomization in the study (to be centrally confirmed). The OctreoScan® should be one that was performed while the patient was on a fixed dose of Octreotide LAR. If a patient has had an OctreoScan® performed while Octreotide LAR treatment-naïve, the patient must have a repeat OctreoScan® performed after 3 months of Octreotide LAR treatments before entering the clinical study to prove that the index lesions or new lesions still meet the criteria for inclusion. It is acceptable to have patients temporarily switched to Octreotide s.c. (up to six weeks) in order to obtain an OctreoScan®, provided they return to the same fixed dose of Octreotide LAR prior to the scan. 7. The tumour uptake observed in each target lesion (for target/nontarget/measurable lesions definition see §Appendix 2, Sections 1 and 2, RECIST Criteria, Version 1.1) using OctreoScan® must be = normal liver uptake observed on planar imaging (to be centrally confirmed) (§Appendices 5 and 6). 8. Karnofsky Performance Score (KPS) ?60. 9. Presence of at least 1 measurable site of disease. 10. [Applicable only for France] All patients included in the trial must be affiliated with a social security regime or be a beneficiary of the same in order to be included in the study. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250
Exclusion criteria
Exclusion criteria: 1. Either serum creatinine >150 µmol/L (>1.7 mg/dL), or creatinine clearance 3 x ULN. 4. Serum albumin 30 mg Octreotide LAR at 3-4 weeks intervals within 12 weeks prior to randomization in the study. 8. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study. 9. Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to randomization in the study. 10. Interferons, Everolimus (mTOR-inhibitors) or other systemic therapies within 4 weeks prior to randomization in the study. 11. Known brain metastases, unless these metastases have been treated and stabilized for at least 24 weeks, prior to enrollment in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to randomization in the study. 12. Uncontrolled congestive heart failure (NYHA II, III, IV). 13. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2 ULN. 14. Any patient receiving treatment with short-acting Octreotide, which cannot be interrupted for 24 h before and 24 h after the administration of 177Lu-DOTA0-Tyr3-Octreotate, or any patient receiving treatment with Octreotide LAR, which cannot be interrupted for at least 6 weeks before the administration of 177Lu-DOTA0-Tyr3-Octreotate, unless the tumour uptake on target lesions observed by OctreoScan® imaging during continued Octreotide LAR treatment is at least as high as normal liver uptake observed by planar imaging (§Appendices 5 and 6). 15. Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study. 16. Prior external beam radiation therapy to more than 25% of the bone marrow. 17. Current spontaneous urinary incontinence. 18. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and proven no evidence of recurrence for 5 years. 19. Patients who have not provided a signed informed consent form to participate in the study, obtained prior to the start of any protocol related activities. 20. Patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Progression Free Survival (PFS) after treatment with 177Lu-DOTA0-Tyr3-Octreotate plus best supportive care (30 mg Octreotide LAR) to treatment with high dose (60 mg) Octreotide LAR in patients with inoperable, progressive (as determined by RECIST Criteria), somatostatin receptor positive, well-differentiated neuroendocrine tumours of the small bowel (midgut carcinoid tumours). ; Secondary Objective: • To compare the Objective Response Rate (ORR) between the two study arms; • To compare the Overall Survival (OS) between the two study arms; • To compare the Time to Tumour Progression (TTP) between the two study arms; • To evaluate the safety and tolerability of 177Lu-DOTA0-Tyr3-Octreotate; • To evaluate the health related quality of life (QoL) as measured by the EORTC QLQ-G.I.NET21 questionnaire; ;Primary end point(s): The primary efficacy variable of this study is PFS measured from the randomization date.;Timepoint(s) of evaluation of this end point: PFS is defined as the time from randomization to documented centrally assessed progression according to RECIST Criteria or death due to any cause, as evaluated by the Independent Review Committee, i.e. the time from randomization until the date of last evaluable tumour assessment or date of death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy variables are: Objective Response Rate (ORR), Time to Tumour Progression (TTP) and Overall Survival (OS). ; Timepoint(s) of evaluation of this end point: Response rates and 95% CIs will be calculated for the ORR by treatment group. Frequencies in the two treatment groups will be compared by Fisher’s exact test. TTP is defined as the time (number of days) from randomization to objective tumour progression centrally assessed. OS is defined as the time from the date of randomization to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off. | — |
Countries
Austria, Belgium, France, Germany, Italy, Portugal, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactJamie Chorlton
Linical Accelovance Europe
Outcome results
None listed