RecruitingPhase 3NCT05387603

Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors. An Open-label, Multicenter, Randomized Phase III Trial Comparing Safety and Efficacy of Personalized Versus Non-personalized Radionuclide Therapy With 177Lu (Lutetium)-DOTATOC.


Sponsor

Lund University Hospital

Enrollment

300 participants

Start Date

Nov 1, 2022

Study Type

INTERVENTIONAL

Conditions

Summary

There are several ways of personalizing PRRT (peptide receptor radionuclide treatment) in NEN (neuroendocrine neoplasia). Nevertheless, the current treatment regimen is not personalized. This trial aims to compare personalized PRRT to non-personalized PRRT in terms of safety, efficacy and resource demands in order to optimize treatment outcomes in an evidence-based manner in future.


Eligibility

Min Age: 18 Years

Inclusion Criteria12

  • 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 Criteria7

  • 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.

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Interventions

DRUG177Lu-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.

DRUGCapecitabine

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.


Locations(4)

Sahlgrenska University Hospital, Dept. of Oncology

Gothenburg, Sweden

Skåne University Hospital, Dept. of Oncology

Lund, Sweden

Karolinska University Hospital, Dept. of Oncology

Stockholm, Sweden

Accademical Hospital, Uppsala, Dept. of Oncology

Uppsala, Sweden

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NCT05387603


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