| Eligibility |
Inclusion Criteria:
- Subjects affected by histologically proven, somatostatin-receptor positive,
progressive, nonresectable, liver-dominant metastatic GEP, bronchial or unknown
primary tumors, G1, G2 and G3, according to the new WHO classification of 2017.
1. Ability to understand and willingness to sign a written informed consent document
2. Aged 18 years or older
3. Histologically proven or cytologically confirmed, non-resectable,GEP, bronchial
or unknown primary NETs with liver-dominant disease with or without prior
treatment with embolization
4. Measurable disease as defined by RECIST 1.1 with at least one dimension = 1.0 cm
5. GEP or unknown primary NET of grade 1, 2 and 3 according to WHO 2017, typical or
atypical lung carcinoid according to the Travis classification of 2004
6. Progression of disease defined by one of the following occurring within 6 months
of study entry:
1. At least a 20% increase in radiologically or clinically measurable disease;
2. Appearance of any new lesion;
3. Symptomatic disease (including worsening hormonal symptoms or symptoms
related to tumor burden);
7. Overexpression of somatostatin receptors of the target lesions at 68Ga-DOTATATE
PET/CT with SUV of lesions greater than normal liver at least in 1 metastasis.
8. ECOG performance status 0 or 1 (Karnofsky = 70%).
9. Women of childbearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation.
10. Previous local therapy (e.g., chemoembolization or bland embolization) is allowed
if completed >6 weeks prior to study entry. For such patients, there must be
either progression of measurable disease documented within the treatment field,
or measurable progressive disease outside the treatment field prior to study
entry.
11. Previous oral chemotherapy, biotherapy (such as Interferons or Everolimus) and/or
investigational agents are allowed if completed >4 weeks prior to study entry For
patients who received systemic therapy prior to study entry, there must be
documented progression of measurable disease since receiving systemic therapy
prior to study entry.
12. Patients must not be candidate for potentially curative surgery. Prior surgery is
allowed no less than 6 weeks prior to study entry. Note: Patients who have
disease that is amendable to resection but who are not a surgical candidate for
other medical reasons would be permitted.
Exclusion Criteria:
1. Women who are pregnant or breastfeeding
2. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 177Lu-DOTATATE as assessed from medical records.
3. Life expectancy < 6 months as assessed by the treating physician.
4. Over 80% liver involvement by tumor per the judgement of the radiologist
5. Poorly differentiated neuroendocrine neoplasms (Neuroendocrine Carcinoma), small and
large cell type; Mixed Neuroendocrine-Nonneuroendocrine Neoplasm (MiNEN).
6. Presence of somatostatin receptor negative lesions.
7. Prior treatment with other radiolabeled somatostatin analogs.
8. Prior systemic chemotherapy, except oral chemotherapy with capecitabine + temozolomide
9. Contraindication to angiography/embolization including:
1. Patients cannot receive contrast
2. Severe allergic reaction to contrast despite premedication. Patients in who IV
contrast is contraindicated are recommended to have MRI abdomen and noncontrast
chest CT scan.
3. Poor renal function not on dialysis
4. Other, based on judgment of the investigator
10. Main portal vein tumor thrombus.
11. Deteriorated renal function:
1. Serum creatinine >1.7 mg/dL OR
2. EGFR <30 ml/min
12. Deteriorated bone marrow function:
1. Hb <8.0 g/dL;
2. WBC <3000/mm3;
3. ANC<1500/mm3;
4. Platelets <75.000/mm3
13. Deteriorated liver function:
1. INR > 2.0 for patients that are not on Coumadin or Xarelto
2. PTT > 2x ULN
3. Total bilirubin >3 mg/dl
4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
14. Clinically relevant toxicities from prior therapies that have not resolved to grade 1
or grade 0
15. Previous liver radioembolization with 90Y-microspheres.
16. Known brain metastases and/or carcinomatous meningitis, unless these metastases have
been treated and stabilized.
17. Uncontrolled diabetes mellitus
18. Inability to interrupt short-acting Octreotide for 24 h before and 24 h after the
administration of 177Lu-DOTATATE; inability to have an interval between Octreotide LAR
and 177Lu-DOTATATE of =4 weeks
19. 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.
20. Prior external beam radiation therapy involving >25% of the bone marrow.
21. Unmanageable urinary incontinence rendering the administration of 177Lu-DOTATATE
unsafe
22. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in
situ of the uterine cervix, unless definitively treated and with no evidence of
recurrence.
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