Patients with SSTR+, advanced, progressive NET Grade 1-3 of any origin for whom Peptide-receptor radionuclide therapy, PRRT, is considered the most appropriate treatment option in relation to other approved or available investigational agents for the specific tumor subtype. MedDRA version: 21.0 Level: LLT Classification code 10062476 Term: Neuroendocrine tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Xeloda
Product Name: Xeloda
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Capecitabine
CAS Number: 154361-50-9
Other descriptive name: CAPECITABINE
Concentration unit: mg/m2
Sponsors
Region Skåne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The subject has given written informed consent to participate in the study. 2. Age =18 years 3. ECOG performance status 0-1 4. Life expectancy > 3 months. 5. Presence of histologically confirmed, advanced, well-differentiated, inoperable NETof any primary tumor origin (except pheochromocytoma and paraganglioma) and any grade, with a maximum Ki67 of 50% 6. SSTR-expression (mean SUV) in tumor lesions = 2x mean SUV in normal liver on 68Ga-DOTA-PET performed = 3 months prior to randomization. Due to partial volume effects, tumor lesions smaller than 1 cm on CT or MRI should not be used to evaluate this eligibility criterium. 7. Radiologically progressive disease within the last 1-24 months according to common clinical criteria and confirmed by the institutional multidisciplinary conference for the treatment of NETs. The CT/MRI that shows tumor progression compared to screening/baseline must have been performed 1-24 months earlier. 8. All previous anti-tumor treatment except SSA must be terminated at least 4 weeks before start of treatment within the trial 9. Measurable disease according to RECIST v 1.1 10. Given the available, approved anti-tumor treatments and the specific characteristics of the patient and the tumor, the investigator judges PRRT to be the treatment of choice 11. GFR > 50 ml/min/1.73 m2 as determined by iohexol- or 51Cr-EDTA clearance, calculated according to a combination of LMR18 and CAPA formulas, or equally accurate method 12. Adequate hematological parameters as defined by: Hemoglobin > 90 g/L, platelets >100 x109/L, leukocytes > 3.0x109/L, neutrophils > 1.5 x109/L 13. Adequate hepatic function as defined by ASAT/ALAT 25 g/L. 14. For women of child-bearing potential, highly effective contraception should be usedfrom the time of inclusion up to at least six months after the EOT visit. For details see appendix 5. 15. For male subjects living with a woman of child-bearing potential, adequate contraception should be used from the time of inclusion up to at least six months after the EOT visit. Adequate male contraception methods are vasectomy, surgical or pharmacological castration, or the use of condom during heterosexual intercourse. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 220
Exclusion criteria
Exclusion criteria: 1. Pregnancy or lactation 2. Previous treatment with PRRT for NET 3. Concomitant systemic anti-tumor therapy other than SSA 4. Participation or recent participation in a clinical study with an investigational product within 30 days of randomization. 5. Known hypersensitivity to edotreotide, octreotide, capecitabine or any of the excipients included in the preparations. 6. Contraindications for treatment with capecitabine: a. Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion. b. New York Heart Association (NYHA) Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure c. Previous serious or unexpected reactions to fluoropyrimidine treatment d. Known complete deficiency of dihydropyrimidine dehydrogenase (DPD) e. Recent or concomitant treatment with brivudine 7. Discordance between CT/MRI/18F-FDG-PET and 68Ga-DOTA-PET, with evidence of tumor lesions without uptake on 68Ga-DOTA-PET 8. Liver-directed therapy of metastases (i.e. radioembolization, chemoembolization, radiofrequency ablation, surgery, etc) 50% of the red bone marrow. 11. Any other serious, uncontrolled medical or psychiatric condition including other advanced or metastatic malignant disease that, in the opinion of the investigator, precludes the patient from participation in the trial 12. Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation 13. Inability or reluctance to adhere to the radiation safety instructions
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to compare the efficacy of personalized vs nonpersonalized PRRT with 177Lu-DOTATOC in patients with SSTR-positive NET G1-G3.;Secondary Objective: The secondary objectives of this study are: 1. To compare the safety of personalized vs non-personalized PRRT 2. To compare OS in personalized vs non-personalized PRRT 3. To compare PFS in personalized vs non-personalized PRRT in the following subgroups: 4. FDG-PET negative patients 5. FDG-PET-positive patients 6. To compare tumor shrinkage at time of best response between personalized vs nonpersonalized PRRT 7. To compare quality-of-life of personalized vs non-personalized PRRT 8. To compare cumulative AD to target tumors in patients with CR, PR, SD, and PD, respectively. 9. To study whether there is a correlation between cumulative median AD to target tumor lesions, and time to progression. 10. To compare AD and BED to kidneys, and rate of renal toxicity, between the two treatment arms 11. To compare health economic parameters between the two treatment arms;Primary end point(s): Median PFS defined as time from randomization to radiological progression, or death from any cause;Timepoint(s) of evaluation of this end point: Radiological evaluation will be performed at screening to confirm progressive disease within the last 24 months. This examination will serve as the baseline evaluation and must therefore be performed within four weeks of randomization. During the treatment phase disease status will be re-evaluated radiologically after every two cycles, and shortly before the EOT visit. During LTFU radiological evaluation will be performed every 3 months during the first year, and every three to six months thereafter, until progression, death, or withdrawal from the trial for any reason. All patients included in the trial will be followed for overall survival every 6 months until End of Trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of treatment-related adverse reactions graded according to CTCAE v5.0 2. Median OS defined as time from randomization to death from any cause 3. Median PFS defined as time from randomization to radiological progression, or death from any cause 4. Percent change in SLD from baseline to time of best response 5. EORTC QoL-questionnaires GI-NET21 6. Cumulative median AD to target tumor lesions in subjects with CR, PR, SD and PD as best response, according to RECIST evaluations 7. Correlation between cumulative median AD to target tumor lesions and time to progression, defined as time from randomization to radiological progression. 8. Cumulative median AD and BED to kidneys vs rate of grade 3-4 renal toxicity (estimated and measured GFR) 9. Differences in resource utilization and treatment cost between the two treatment arms, in relation to the respective mPFS and mOS.;Timepoint(s) of evaluation of this end point: Continuously: Rate of AEs, survival Every two cycles during treatment phase and every 3-6 months during LTFU: RECIST evaluations of radiological response (CR, PR, SD, PD, PFS, SLD) Every two cycles, and in EOT and EOS visit: QoL In every treatment cycle: AD and BED to tumor and kidneys, resource utilization | — |
Countries
Sweden
Contacts
Public ContactPernilla Asp
Region Skåne
Outcome results
None listed