Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors. (START-NET)

Lund University Hospital

Status and phase: Enrolling; Phase 3

Conditions: Neuroendocrine Tumors

Treatments: Drug: 177Lu-DOTATOC; Drug: Capecitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT05387603

2021-002218-15 (EudraCT Number)

START-01

Details and patient eligibility

About

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.

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 3 patient groups

177Lu-DOTATOC + Capecitabine

Experimental group

Description:

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. .

Treatment:

Drug: Capecitabine

Drug: 177Lu-DOTATOC

177Lu-DOTATOC

Experimental group

Description:

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.

Treatment:

Drug: 177Lu-DOTATOC

Standard 177Lu-DOTATOC

Active Comparator group

Description:

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

Treatment:

Drug: 177Lu-DOTATOC