LUTETIUM (177LU) EDOTREOTIDE for Neuroendocrine tumours

Inclusion criteria

• {"criterion_text":"- The subject has given written informed consent to participate in the study.\n- 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\n- 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\n- Adequate hematological parameters as defined by: Hemoglobin > 90 g/L, platelets >100 x109/L, leukocytes > 3.0x109/L, neutrophils > 1.5 x109/L\n- Adequate hepatic function as defined by ASAT/ALAT < 3 x ULN, bilirubin < 2 x ULN, albumin > 25 g/L.\n- 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.\n- 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.\n- Age ≥18 years\n- ECOG performance status 0-1\n- Life expectancy > 3 months.\n- Presence of histologically confirmed, advanced, well-differentiated, inoperable NET of any primary tumor origin (except pheochromocytoma and paraganglioma) and any grade, with a maximum Ki67 of 50%\n- SSTR-expression (mean SUV) in tumor lesions ≥ 2x mean SUV in normal liver on 68Ga-DOTA-PET performed ≤ 6 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.\n- 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.\n- All previous anti-tumor treatment except SSA must be terminated at least 4 weeks before start of treatment within the trial\n- Measurable disease according to RECIST v 1.1"}

Exclusion criteria

• {"criterion_text":"- Pregnancy or lactation\n- Previous radiotherapy of any kind which has resulted in irradiation of both kidneys and/or > 50% of the red bone marrow.\n- 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\n- Mental inability, reluctance or language difficulties that result in difficulty understanding the meaning of study participation\n- Inability or reluctance to adhere to the radiation safety instructions\n- Previous treatment with PRRT for NET\n- Concomitant systemic anti-tumor therapy other than SSA\n- Participation or recent participation in a clinical study with an investigational product within 30 days of randomization.\n- Known hypersensitivity to edotreotide, octreotide, capecitabine or any of the excipients included in the preparations.\n- 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\n- Discordance between CT/MRI/18F-FDG-PET and 68Ga-DOTA-PET, with evidence of tumor lesions without uptake on 68Ga-DOTA-PET\n- Liver-directed therapy of metastases (i.e. radioembolization, chemoembolization, radiofrequency ablation, surgery, etc) < 4 weeks prior to randomization.\n- Major surgery < 12 weeks prior to randomization."}

Primary endpoints

• {"endpoint_text":"- Median PFS defined as time from randomization to radiological progression, or death from any cause","definition_or_measurement_approach":"Time from randomization to radiological progression, or death from any cause (radiological progression assessed per protocol imaging schedule)."}

Secondary endpoints

• {"endpoint_text":"- Rate of treatment-related adverse reactions graded according to CTCAE v5.0","definition_or_measurement_approach":"Treatment-related adverse reactions graded according to CTCAE v5.0"}
• {"endpoint_text":"- Median OS defined as time from randomization to death from any cause","definition_or_measurement_approach":"Time from randomization to death from any cause"}
• {"endpoint_text":"- Median PFS defined as time from randomization to radiological progression, or death from any cause","definition_or_measurement_approach":"Time from randomization to radiological progression, or death from any cause"}
• {"endpoint_text":"- Percent change in SLD from baseline to time of best response","definition_or_measurement_approach":"Percent change in sum of longest diameters (SLD) from baseline to time of best response (per RECIST v1.1)"}
• {"endpoint_text":"- EORTC QoL-questionnaires GI-NET21","definition_or_measurement_approach":"Quality of life assessed using EORTC GI-NET21 questionnaires"}
• {"endpoint_text":"- Cumulative median AD to target tumor lesions in subjects with CR, PR, SD and PD as best response, according to RECIST evaluations","definition_or_measurement_approach":"Cumulative median absorbed dose (AD) to target tumor lesions categorized by best RECIST response (CR, PR, SD, PD)"}
• {"endpoint_text":"- Correlation between cumulative median AD to target tumor lesions and time to progression, defined as time from randomization to radiological progression.","definition_or_measurement_approach":"Correlation analysis between cumulative median AD to target lesions and time to progression (time from randomization to radiological progression)"}
• {"endpoint_text":"- Cumulative median AD and BED to kidneys vs rate of grade 3-4 renal toxicity (estimated and measured GFR)","definition_or_measurement_approach":"Comparison of cumulative median AD and biologically effective dose (BED) to kidneys with rate of grade 3-4 renal toxicity using estimated and measured GFR"}
• {"endpoint_text":"- Differences in resource utilization and treatment cost between the two treatment arms, in relation to the respective mPFS and mOS.","definition_or_measurement_approach":"Health economic comparison of resource utilization and treatment costs between arms relative to median PFS and median OS"}

Sweden

Earliest CTIS Part Ii Submission Date

29-04-2024

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

715

Number Of Sites

4

Number Of Participants

300

Primary sponsor

Full Name

Region Skane

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden

Third parties

• {"country":"Sweden","full_name":"Region Skane Skanes Universitetssjukhus","duties_or_roles":"code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}