Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

Phase 3RecruitingNCT05387603

Lund University Hospital300 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

300

Conditions

Neuroendocrine Tumors

Interventions

177Lu-DOTATOCDRUG

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.

CapecitabineDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (4)

Sahlgrenska University Hospital, Dept. of Oncology

Gothenburg, Sweden

RECRUITING

Skåne University Hospital, Dept. of Oncology

Lund, Sweden

RECRUITING

Karolinska University Hospital, Dept. of Oncology

Stockholm, Sweden

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Rate of treatment-related adverse reactions

Treatment-related adverse reactions graded according to CTCAE v.5.0.

Time frame: 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).

Median OS defined as time from randomization to death of any cause.

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

Central Contacts

Pernilla Asp, MD, Senior consultant

CONTACT

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

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.