The main objective of this randomized phase II comparative study is to evaluate the
Progression Free survival (PFS) and the safety as co-primary objective of two different
schedule of administrations of 177lu-dotatate: intensive (every 5 weeks) vs no intensive
(every 8-10 weeks) The secondary objectives are DCR, the late toxicity, OS and dosimetry.
Patients with any tumor histotype documented as sst2-positive in pre-study period will be
enrolled in the study.
The study will include a total of 618 planned patients. They will be randomly assigned to
receive 5 cycles of PRRT at intervals of 5 or 8-10 weeks between cycles.
Inclusion Criteria:
1. Age >18 years.
2. Patients must have histologically or cytologically confirmation of neuroendocrine
tumors or any other tumor histotype documented as sst2-positive), that may benefit
from receptor radionuclide therapy and for which there aren't any other effective
treatments. For cerebral sst2-positive tumors, if biopsy is no feasible for technical
reason or risk benefit balance, patients may be enrolled if CT or MRI strongly suggest
oncological lesion confirming the 68Ga PET-CT dota-peptide SSTr2 positivity..
3. Measurable disease according to RECIST 1.1.criteria also patients without measurable
but with evaluable disease disease can be enrolled.
4. Any disease stage is allowed. Patients with documented disease will be admitted to
therapeutic phase only if the diagnostic OctreoScan (the tumour uptake will be
evaluated with a 3-grade scale, where 1 = liver uptake, 2 > liver uptake and < kidney
uptake and 3 > kidney uptake: only tumour uptakes grade 2 and 3 will be considered for
therapy) and/or Positron Emission Tomography (PET)/CT 68Ga-peptide images demonstrate
a significant uptake in the tumour.
5. Patients with progressive disease in pre-study period (PD within the last 12 months),
refractory to conventional standard treatments; clinical progression is allowed
6. Patients with or without concurrent therapy with somatostatin analogs
7. Life expectancy of greater than 6 months.
8. Eastern Cooperative Oncology Group (ECOG) performance status <2
9. Adequate haematological, liver and renal function: haemoglobin >= 9 g/dL, absolute
neutrophil count (ANC) >= 1.5 x 109 /L, platelets >= 100 x 109 /L, bilirubin ≤1.5 X
upper normal limit (UNL) , alanine aminotransferase ( ALT) and Aspartate
aminotransferase (AST) <2.5 X UNL (< 5 X UNL in presence of liver metastases,
creatinine < 2 mg/dL.
10. If female of childbearing potential highly effective birth control methods, according
to guideline "Recommendation related to contraception and pregnancy testing in
clinical trials", (2014_09_15 section 4.1) are mandatory.
11. Participant is willing and able to give informed consent for participation in the
study.
Exclusion Criteria:
1. Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks and
treated within 2 weeks with palliative radiotherapy, hormonal or biological therapy.
2. Patients treated with previous radio-metabolic therapy with an adsorbed dose to the
kidney more than 23 Gy and more than 1.8 Gy for the bone marrow or as surrogate of
dosimetry (13).
3. All acute toxic effects of any prior therapy (including surgery radiation therapy,
chemotherapy) must have resolved to a grade ≤ 1 according to National Cancer Institute
Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE)
4. ECOG performance status >2
5. Participation in another clinical trial with any investigational agents within 30 days
prior to study screening.
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.
7. Assessed bone marrow invasion > 50% (with Bone Marrow biopsy or instrumental exams i.e
bone scan or CT or MRI)
8. Pregnant or breastfeeding women are excluded from the present study.
