Inclusion Criteria:
1. Patients ≥18 years of age.
2. Participants capable of giving informed consent. 3. Presence of unresectable or metastatic, well differentiated, somatostatin receptor
positive non gastroenteropancreatic neuroendocrine tumours. Or for those having 2
cycles repeat therapy, GEP NET > 18 months from start of previous PRRT.
4. Patients must have progressive disease based on RECIST Criteria, Version 1.1. In
order to make the assessment, two CT (or MRI) scans are required. The oldest scan
must not be older than 3 years from the date of enrolment. The most recent scan must
not be older than 6 weeks from the date of enrolment.
5. Confirmed presence of somatostatin receptors on all target lesions (for
target/non-target/measurable lesions definition see RECIST Criteria, Version 1.1)
documented by CT/MRI scans, based on positive OctreoScan or Ga68 Dotatate PET
imaging within 24 weeks prior to enrolment in the trial.
6. The tumour uptake observed in each target lesion (for target/non-target/measurable
lesions definition see RECIST Criteria, Version 1.1) using OctreoScan/Tc-99m-SRS
should be ≥ normal liver uptake observed on planar imaging.
7. The tumour uptake observed in each target lesion (for target/non-target/ measurable
lesions definition see RECIST Criteria, Version 1.1) using Ga68 Dotatate PET should
be ≥ normal liver uptake observed on PET imaging.
8. KPS ≥60.
9. Presence of at least 1 measurable site of disease on cross-sectional imaging.
10. Females of childbearing potential (defined as <2 years after last menstruation and
not surgically sterile) and males, who are not surgically sterile or with female
partners of childbearing potential must be willing to use a highly effective method
of contraception during treatment and for a minimum of 6 months after the end of
treatment (hormonal or barrier method of birth control; abstinence). Contraceptive
methods that can achieve a failure rate of less than 1% per year when used
consistently and correctly are considered as highly effective birth control methods.
Such methods include:
• combined (estrogen and progestogen containing) hormonal contraception associated
with inhibition of ovulation:
- - progestogen-only hormonal contraception associated with inhibition of
ovulation.
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion. • vasectomised partner. • sexual abstinence.
- - Women of childbearing potential (WOCBP) must have a negative pregnancy
test within 7 days prior to treatment initiation).
NOTE: Participants are
considered not of childbearing potential if they are surgically sterile
(i.e. they have undergone a hysterectomy, bilateral tubal ligation or
bilateral oophorectomy) or they are postmenopausal. Inclusion Criteria for
Subsequent Treatments. 1. Both serum creatinine ≤150 μmol/L (≤1.7 mg/dL) and calculated creatinine clearance
≥40 mL/min, eventually confirmed by measured creatinine clearance (or measured GFR)
using isotopic GFR measurement ≥40 mL/min (the measured creatinine clearance/GFR is
required only as confirmatory exam).
2. Haemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); WBC ≥2 x109/L (≥2000/mm3);
platelets ≥75 x109/L (≥75 x103/mm3).
3. Total bilirubin ≤3x ULN. 4. Serum albumin >3.0 g/dL, or serum albumin ≤3.0 g/dL, but
normal prothrombin time.
5. KPS ≥60.
Exclusion Criteria:
- - Participants will not be eligible for trial participation if they meet any of the
exclusion criteria, or will be discontinued at the discretion of the Investigator if
they develop any of the exclusion criteria during the trial.
Exclusion Criteria at Baseline. 1. Either serum creatinine >150 μmol/L (>1.7 mg/dL), or calculated creatinine clearance
<40 mL/min, eventually confirmed by measured creatinine clearance (or measured GFR
using isotopic GFR measurement) <40 mL/min (the measured creatinine clearance/GFR is
required only as confirmatory exam).
2. Haemoglobin concentration <5.0 mmol/L (<8.0 g/dL); WBC <2 x109/L (2000/mm3);
platelets <75 x109/L (75 x103/mm3).
3. Total bilirubin >3x upper limit of normal (ULN).
4. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.
5. Pregnancy, planning a pregnancy or lactation.
6. Any surgery, radioembolization, chemoembolization, chemotherapy, and radiofrequency
ablation within 12 weeks prior to enrolment in the trial.
7. Interferon, Everolimus (mTOR-inhibitors), or other systemic therapies within 4 weeks
prior to enrolment in the trial.
8. Patients with a history of brain metastases must have a head CT with contrast to
document stable disease prior to enrolment in the trial.
9. Uncontrolled congestive heart failure (NYHA II, III, IV).
10. Uncontrolled diabetes mellitus as defined by a fasting blood glucose >2x ULN.
11. Any participant receiving treatment with short-acting Octreotide, which cannot be
interrupted for 12 hours before and 24 hours after the administration of Lutathera,
or any participant receiving treatment with Octreotide LAR or Lanreotide Autogel,
which cannot be interrupted for at least 28 days before the administration of
Lutathera, unless the tumour uptake observed on target and non-target but measurable
lesions by OctreoScan or Ga68 Dotatate PET imaging during continued Octreotide LAR
or Lanreotide Autogel treatment is at least as high as normal liver uptake observed
by planar imaging (Kwekkeboom, Krenning et al. 2009).
12. Patients with any other significant medical, psychiatric, or surgical condition,
currently uncontrolled by treatment, which may interfere with completion of the
trial.
13. Prior external beam radiation therapy to more than 25% of the bone marrow.
14. Current spontaneous urinary incontinence.
15. Other known co-existing malignancies except non-melanoma skin cancer and carcinoma
in situ of the uterine cervix, unless definitively treated and proven no evidence of
recurrence for 5 years.
16. Patients who have not provided a signed ICF to participate in the trial, obtained
prior to the start of any protocol related activities.
17. Patient with known incompatibility to CT Scans with IV contrast due to allergic
reaction or renal insufficiency. If such participants can be imaged without the use
of CT contrast material (ie, can tolerate MRI scans), such participants would not be
excluded.
18. Patients who have participated in any therapeutic clinical trial/received any
investigational agent within the last 30 days are excluded from participation in
this trial.
19. Patients with hypersensitivity to Lutathera (active substance or any of the
excipients).
20. Involved in the planning or conduct of this trial.
21. Unwilling or unlikely to comply with the requirements of the trial. Exclusion
Criteria for Subsequent Treatments. 1. Exclusion criteria for Baseline # 1, 2, 3, 4, and 10 apply to all subsequent
treatments, when a relationship cannot be excluded with either trial drugs or the
corresponding toxicity has not resolved.
2. In relation to renal function, participants are also excluded from further therapy
in case of >40% increase of serum creatinine over the baseline and with a
concomitant decrease of >40% in creatinine clearance as calculated according to the
Cockroft-Gault method, eventually confirmed by measured creatinine clearance (or
GFR), if a relationship may not be excluded and the corresponding toxicity has not
resolved.
3. When such exclusion criteria events occur, the participant will postpone any
subsequent trial treatment until resolution of the event (normalisation or return to
baseline values). The participant remains in the trial and continues observation
with the scheduled tumour and clinical assessments.
4. All other exclusion criteria for enrolment eligibility apply to all subsequent
treatments.
