Clinical Trial Finder

Inclusion Criteria:

• - Age ≥18 years.

• - Written informed consent.

• - Eastern Cooperative Oncology Group (ECOG) 0-1.

• - Presence of histologically confirmed, advanced, well-differentiated, inoperable neuroendocrine tumors (NET) of any primary tumor origin and any grade, except for pheochromocytoma and paraganglioma.

• - Somatostatine receptor (SSTR)-expression in tumor lesions > basal liver uptake on 68Ga-DOTA-PET.

• - 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.

• - All previous anti-tumor treatment except SSA must be terminated at least 4 weeks before start of treatment within the trial.

• - Measurable disease according to RECIST v 1.1.

• - Given the available, approved anti-tumor treatments and the specific characteristics of the patient and the tumor, the investigator judges peptide receptor radionuclide therapy (PRRT) to be the treatment of choice.

• - 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.

• - Hemoglobin > 90 g/L, platelets >100 x109/L, leukocytes > 3.0x109/L, neutrophils > 1.5 x109/L, aspartate transaminase (ASAT)/alanine aminotransferase (ALAT) < 3 x ULN, bilirubin < 2 x upper limit of normal (ULN), albumin > 25 g/L.

• - For women of child-bearing potential, highly effective contraception should be used from the time of inclusion up to at least six months after the end of treatment (EOT) visit.

Exclusion Criteria:

• - Pregnancy or lactation.

• - Previous treatment with PRRT.

• - Concomitant systemic anti-tumor therapy other than somatostatin analogue (SSA) - Contraindications for treatment with capecitabine according to the approved label.

• - Discordance between CT/MRI/18F-FDG-PET and 68Ga-DOTA-PET, with evidence of tumor lesions without uptake on 68Ga-DOTATOC.

• - Any other serious, uncontrolled medical or psychiatric condition that, in the opinion of the investigator, precludes the patient from participation in the trial.

• - Unwillingness, or inability, to participate in any part of the trial procedures or treatments.

Arms

Experimental: 177Lu-DOTATOC + Capecitabine

Patients with 68Ga-DOTA- and 18F-FDG-PET-positive NET will receive a combination of intravenous 7.5 GBG (gigabequerel) 177Lu-DOTATOC for about 7 cycles in combination with capecitabine (4 cycles, cycle length 3 weeks, with one week without capecitabine, dosing 825 mg twice daily) and PRRT to a cumulative renal AD (absorbed dose) limit of 30 Gy and dosimetry-based PRRT. .

Experimental: 177Lu-DOTATOC

Intravenous infusion for about 7 treatment cycles with 7.5 GBq 177Lu-DOTATOC with an interval of 10 ± 2 weeks and PRRT to a cumulative renal AD limit of 30 Gy and dosimetry-based PRRT.

Active Comparator: Standard 177Lu-DOTATOC

Standard treatment of 177Lu-DOTATOC with treatment for 4 cycles.

Interventions

Drug: - 177Lu-DOTATOC

The investigational medicinal product (IMP) is 177Lu-DOTATOC which is registered as an orphan drug by the EMA ( European Medicines Agency) for the treatment of GEP-NEN (gastro-entero-pancreatic neuroendocrine tumor). The IMP will be administered to participants both in the control arm and the experimental arms, but with different intervals, but the same activity; 7.5 Gbq per dosing.

Drug: - Capecitabine

Will be given orally with a dose of 825/m2 twice daily, starting on day 1 of each of the 4 first treatment cycles, cycle length 3 weeks.