Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

NCT05387603 | Recruiting Phase 3 DMC

• 2 other identifiers: START-012021-002218-15
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Neuroendocrine Tumors

Keywords

Neuroendocrine tumors; Radionuclide therapy; Personalized radionuclide therapy; 177Lu-DOTATOC; Capecitabine; Dosimetry-based radionuclide therapy; Somatostatin receptor; Lutetium; Beta- and gamma-emitting radionuclide; Translational research

Outcome Measures

Primary Outcomes (3)

• Median progression free survival (PFS) defined as time from randomization to radiological progression.

  Time to progression is evaluated by CT (computed tomography) or MRI (magnetic resonance imaging) after every 16-22 weeks.

  Before start of treatment (within 4 weeks), then every 10 +/- 2 weeks weeks, at follow up (every 3-6 month (investigators choice) until progression.

• Median progression free survival (PFS) defined as time from randomization to radiological progression.

  Time to progression is evaluated by CT (computed tomography) or MRI (magnetic resonance imaging) after every 10 +/- 2 weeks.

  Before start of treatment (within 4 weeks), then every 10 +/- week at follow up (every 3-6 month (investigators choice) until death.

• Median progression free survival (PFS) defined as time from randomization to radiological progression,

  Time to progression is evaluated by CT (computed tomography) or MRI (magnetic resonance imaging) after every 16-22 weeks.

  Before start of treatment (within 4 weeks), then every 10 +/- 2 weeks, at follow up (every 3-6 month (investigators choice) or patients withdrawal of concent.. No end can be given.

Secondary Outcomes (9)

• Rate of treatment-related adverse reactions

  At every treatment cycle, cycle length is 10 +/-2 weeks, at treatment follow up every 3-6 month (investigators choice) until progression. No time point can be given.

• Median overall survival (OS).

  From date of randomization until the date of death. Timepoint unknown, as date of death can´t be predicted.

• Progression free survival.

  From time of randomization until the date of first documented progression. Is evaluated within 4 weeks before randomization, after each treatment, every 10 +/2 weeks. Timepoint unknown, as date of progression can´t be predicted.

• Percent change in sum of longest diameters (SLD) of tumor lesions.

  At each radiological investigation with CT or MRI of thorax and abdomen. Is done every 10 +/- 2 weeks. In the follow up period, evaluations are done every 3-6 months until death.

• Quality of Life as judged by the patient.

  Patients complete the QoL forms before start of treatment, at cycle 2 (cycle length 10+/-2 weeks), at each treatment cycle (4-approximately 7), until progression.

Study Arms (3)

177Lu-DOTATOC + Capecitabine

EXPERIMENTAL

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. .

Drug: 177Lu-DOTATOC; Drug: Capecitabine

177Lu-DOTATOC

EXPERIMENTAL

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.

Drug: 177Lu-DOTATOC

Standard 177Lu-DOTATOC

ACTIVE COMPARATOR

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

Drug: 177Lu-DOTATOC

Interventions

177Lu-DOTATOC DRUG

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.

177Lu-DOTATOC; 177Lu-DOTATOC + Capecitabine; Standard 177Lu-DOTATOC

Capecitabine DRUG

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.

177Lu-DOTATOC + Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lund University Hospital: lead

Study Sites (4)

Sahlgrenska University Hospital, Dept. of Oncology

Gothenburg, Sweden

RECRUITING

Skåne University Hospital, Dept. of Oncology

Lund, SE-226 52, Sweden

RECRUITING

Karolinska University Hospital, Dept. of Oncology

Stockholm, SE-171 76, Sweden

RECRUITING

Accademical Hospital, Uppsala, Dept. of Oncology

Uppsala, SE-752 37, Sweden

RECRUITING

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

177Lu-octreotide, DOTA(0)-Tyr(3)-; Capecitabine

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Pernilla Asp, MD, Senior consultant

CONTACT

+46 46 17 75 20; pernilla.p.asp@skane.se

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized, open-label, controlled trial in which patients are assigned to either non-personalized treatment with 4 cycles of 7.5 gigabequerel (GBq) 177Lu-DOTATOC (TOC), or personalized treatment based on dual imaging. In the personalized arm patients are treated according to the results of the dual imaging at screening: A. Patients with 68Ga-1,4,7,10-tetra-azacyclododecane-N.n,N,N-tetraacetic acid (DOTA)-positron emission tomography (PET)-positive but 18F-2-fluoro-2-deoxy-D-glucosefluorodeoxyglucose (FDG)-PET-negative NET will receive dosimetry-based PRRT only (dTOC) B. Patients with 68Ga-DOTA- and 18F-FDG-PET-positive NET will receive a combination of capecitabine and dosimetry-based PRRT (CAP-dTOC).

Study Record Dates

• First Submitted: April 21, 2022
• First Posted: May 24, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4)