Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

Neuroendocrine Tumors Clinical Trial

— START-NET  

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05387603
• Other study ID #: START-01
• Secondary ID: 2021-002218-15
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 1, 2022
• Est. completion date: October 2025

Study information

• Verified date: March 2024
• Source: Lund University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Est. completion date: October 2025
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuroendocrine Tumors

Intervention

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.
• 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.

Locations

Country	Name	City	State
Sweden	Sahlgrenska University Hospital, Dept. of Oncology	Göteborg
Sweden	Skåne University Hospital, Dept. of Oncology	Lund
Sweden	Karolinska University Hospital, Dept. of Oncology	Stockholm
Sweden	Accademical Hospital, Uppsala, Dept. of Oncology	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Lund University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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	Rate of treatment-related adverse reactions	Treatment-related adverse reactions graded according to CTCAE v.5.0.	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.
Secondary	Median overall survival (OS).	Median OS defined as time from randomization to death of any cause.	From date of randomization until the date of death. Timepoint unknown, as date of death can´t be predicted.
Secondary	Progression free survival.	Median progression free survival (PFS).	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.
Secondary	Percent change in sum of longest diameters (SLD) of tumor lesions.	Percent change in SLD from baseline (within 4 weeks before treatment) to time of best response.	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.
Secondary	Quality of Life as judged by the patient.	All patients complete the Eastern Cooperative Oncology Group (EORTC) QoL (quality of life)-questionnaires GI- neuroendocrine tumors (NET)21.	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.
Secondary	Cumulative median absorbed dose (AD)	AD to target tumor lesions in subjects with complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) as best response, according to RECIST evaluations.	After each dosimetry measurements after each treatment cycle (cycle length 10 +/2 weeks), up to 18 +/-2 months.
Secondary	Correlation between cumulative median absorbed dose and time to progression.	Correlation between cumulative median absorbed dose to target tumor lesions and time to progression, defined as time from randomization to radiological progression.	Every 10 +/- 2 weeks up to 18 +/- 2 months.
Secondary	Cumulative median absorbed dose (AD) and biological effective dose to kidneys.	Cumulative median AD and biological effective dose (BED) to kidneys vs rate of grade 3-4 renal toxicity (estimated and measured GFR ( glomerular filtration rate).	Is evaluated with dosimetry after each treatment, 10 +/- 2 weeks, up to 18 +/- 2 months.
Secondary	Differences in resource utilization and treatment cost.	Differences in resource utilization and treatment cost between the two treatment arms, in relation to the progressive free survival (PFS) and overall survival (OS).	Through study completion, an average of 18 months, assessed every 10 +/- 2 weeks by questionnaires.