- - Histological or cytological diagnosis of neoplasia (not mandatory for meningioma)
- GEPNETs grade 3 or aggressive grade 2 tumours with a poor prognosis and a Ki67 > 15%
OR neuroendocrine tumours NOS after standard therapy OR thymomas/tumours of other
origin after standard therapy OR meningiomas after standard therapy not suitable for
surgery or radiotherapy.
- - Evidence of regional or distant metastases or localised disease not accessible for
- - Measurable disease according to RECIST 1.1.
- - Evidence of somatostatin receptor positive disease detected by 68Ga-DOTA-TATE/TOC PET.
- - Progressive disease during the last 14 months based on CT or new lesions detected by
- - Performance status ECOG 0 - 1.
- - Life expectancy > 6 months.
- - Age >18 years, no upper age limit.
- - Neutrophil count >1,5 x 109/L.
- - Platelet count >100 x 109/L.
- - Normal liver function regarding transaminases, PK and albumin.
A raised bilirubin
which can be considered an isolated effect of liver metastases is not a
contraindication as long as the levels remain <1.5 x ULN.
- - Written informed consent from patients.
- - Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal subjects.
Women will be considered post-menopausal if they have
been amenorrheic for 12 months without an alternative medical cause. The following
age-specific requirements apply:
- - Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
- - Women ≥50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
- - Performance Status ECOG > 1.
- - Well differentiated GEPNETs grad 1 and 2 (except aggressive grade 2 tumours with a
poor prognosis and a Ki67 > 15%)
- Loco-regional treatment during the last 3 months involving all of the measurable
- - Chemotherapy during the last 8 weeks or longer until no persisting toxicity exists.
Earlier treatment with mTORi or TKI the last 4 weeks or until no persisting toxicity
- - Previous treatment with 177Lu-DOTA-TATE or cis-/carboplatin.
- - Other concomitant nephrotoxic treatment.
- - Serious heart disease (NYHA III-IV)
- Previous radiotherapy including >25% of active bone marrow volume.
- - Pregnancy and lactation.
- - Extensive liver metastases combined with impaired liver function (i.e. abnormal
laboratory parameters (> grad 1 CTCAE) or ascites)
- Symptomatic CNS metastases (e.g. requiring corticosteroid treatment) Symptomatic
treatment for meningiomas or corticosteroids due to treatment related swelling is
- - Ongoing treatment with interferon.
This treatment should be suspended a minimum of 4
wees before treatment with 177Lu-DOTA-TATE, or longer if there is persisting signs of
- - Patients who have a another metastatic tumor diagnosis.
- - Known or expected hypersensitivity to 177Lu-DOTA-TATE, 68Ga- DOTA-TATE/TOC or any of
- - History of psychiatric disease/condition that may interfere with the objectives and
assessments of the study.
- Female subjects who are pregnant or breastfeeding or subjects of reproductive
potential who are not willing to employ effective birth control methods (Pearl index
<1) from screening to 6 months after the last dose of olaparib