Peptide Receptor Radionuclide Therapy (PRRT) in Tumors With High Expression of Somatostatin Receptors (Phase 2) (FENET-2016)

University Hospital of Ferrara

Status: Unknown

Conditions: Neuroendocrine Tumors; Peptide Receptor Radionuclide Therapy (PRRT)

Treatments: Radiation: Re-treatment 177Lu-DOTATOC; Radiation: Re-treatment 90Y-DOTATOC; Radiation: Lutetium-177 (177Lu)-DOTATOC; Radiation: Yttrium-90 (90Y)-DOTATOC; Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Study type: Interventional

Funder types: Other

Identifiers

NCT04790708

2016-005129-35 (EudraCT Number)

160990

Details and patient eligibility

About

The rationale behind the purpose of this study lays on:

• the evidence that PRRT could represent a valuable treatment for the majority of patients with neuroendocrine tumor (NET) in disease progression, operated or inoperable, presenting lesions expressing somatostatin receptors and for which standard treatments are not already available;
• the current impossibility of acquiring on the market radiolabelled analogues of somatostatin used for PRRT with marketing authorisation;
• the need to collect a larger case history than in previous studies;
• the need to stratify the various histotypes based on the response obtained;
• the need to define new treatment schemes that guarantee the maximum efficacy and the lowest possible toxicity - with low cumulative (and per cycle) activities radiopharmaceutical and according to the concept of dose hyperfractionation - with a view to an optimal balance between risk and benefit.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 1. Age ≥18 years, of both sexes, of any ethnicity;
• 2. Cyto-histological and immunohistochemical diagnosis of NET;
• 3. Evaluation of the cell proliferation index by studying Ki-67 and / or E3 ubiquitin-protein ligase (MIB-1).
• 4. Illness measurable according to RECIST 1.1 criteria by imaging conventional (CT with contrast medium or MRI with contrast medium) not earlier than two months with respect to enrollment;
• 5. Elevated expression of somatostatin receptors documented by PET-CT with 68Ga-DOTATOC in the target lesion (s). It is defined as "high expression of somatostatin receptors "a ratio of Maximum standardized uptake value (SUVmax) lesion / Mean standardized uptake value (SUVmean) muscle ≥ 4: 1 calculated with semi-quantitative analysis on examination PET-CT with 68Ga-DOTATOC;
• 6. Dosage of Chromogranin A (and any other specific markers) not prior to two months of enrollment;
• 7. Evaluation of glucose metabolism in the target lesion (s) by PET-CT with 18F-FDG;
• 8. Preserved haematological, hepatic and renal parameters, in particular: white blood cells ≥2500 / μL; platelets ≥ 90000 / μL; hemoglobin ≥ 9 gr / dL; creatinine ≤ 2 mg / dL; bilirubin ≤ 2.5 mg / dL
• 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
• 10. Life expectancy ≥ 6 months;
• 11. Stable or progressive disease, at any stage, both in operated patients that inoperable;
• 12. Absence of standard treatments already documented and of equal effectiveness;
• 13. Absence of surgical, chemotherapy and / or radiotherapy treatments for at least 30 days. On the other hand, patients in therapy with somatostatin analogues or biologics, such as mechanistic target of rapamycin (m-TOR) inhibitors;
• 14. Voluntary participation in the study by signing the consent form informed, after reading and complete understanding of the information notes.

Exclusion criteria

• 1. Lack of the requirements listed above;
• 2. State of pregnancy;
• 3. Breastfeeding and relative refusal to suspend breastfeeding;
• 4. Participation in another therapeutic experimental clinical protocol in the four weeks prior to the PRRT;
• 5. Bone marrow invasion of disease> 25% confirmed;
• 6. Previous extensive radiotherapy treatments.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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250 participants in 6 patient groups

Midgut NETs

Experimental group

Description:

75 patients affected by non-functional and functional NETs arising from: stomach, duodenum, jejunum, ileum, colon and rectum.

Treatment:

Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Radiation: Re-treatment 177Lu-DOTATOC

Radiation: Re-treatment 90Y-DOTATOC

Radiation: Lutetium-177 (177Lu)-DOTATOC

Radiation: Yttrium-90 (90Y)-DOTATOC

Pancreatic NETs

Experimental group

Description:

75 patients affected by non-functional and functional NETs arising from Pancreas.

Treatment:

Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Radiation: Re-treatment 177Lu-DOTATOC

Radiation: Re-treatment 90Y-DOTATOC

Radiation: Lutetium-177 (177Lu)-DOTATOC

Radiation: Yttrium-90 (90Y)-DOTATOC

Bronchial NETs

Experimental group

Description:

25 patients affected by non-functional and functional Bronchial NETs.

Treatment:

Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Radiation: Re-treatment 177Lu-DOTATOC

Radiation: Re-treatment 90Y-DOTATOC

Radiation: Lutetium-177 (177Lu)-DOTATOC

Radiation: Yttrium-90 (90Y)-DOTATOC

Sympathetic-Adrenergic axis NEts

Experimental group

Description:

25 patients affected by non-functional and functional: Pheochromocytoma, Paraganglioma and Neuroblastoma

Treatment:

Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Radiation: Re-treatment 177Lu-DOTATOC

Radiation: Re-treatment 90Y-DOTATOC

Radiation: Lutetium-177 (177Lu)-DOTATOC

Radiation: Yttrium-90 (90Y)-DOTATOC

Other Nets

Experimental group

Description:

25 patients affected by non-functional and functional NETs arising from Skin, Thyroid (medullary thyroid and anaplastic cancer) and Parathyroids.

Treatment:

Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Radiation: Re-treatment 177Lu-DOTATOC

Radiation: Re-treatment 90Y-DOTATOC

Radiation: Lutetium-177 (177Lu)-DOTATOC

Radiation: Yttrium-90 (90Y)-DOTATOC

Cancers of Unknown Primary Origin (CUP) NETs

Experimental group

Description:

25 patients affected by non-functional and functional unknown primary NETs

Treatment:

Radiation: 177Lu-DOTATOC + 90Y-DOTATOC

Radiation: Re-treatment 177Lu-DOTATOC

Radiation: Re-treatment 90Y-DOTATOC

Radiation: Lutetium-177 (177Lu)-DOTATOC

Radiation: Yttrium-90 (90Y)-DOTATOC