Clinical Trial Finder

Inclusion Criteria:

• - 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 complete resection.

• - 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 68Ga-DOTA-TATE PET.

• - 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.

• - GFR > 50 ml/min.

• - 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 hysterectomy).

Exclusion Criteria:

• - 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 lesions.

• - 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 exists.

• - 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 however allowed.

• - 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 toxicity.

• - Patients who have a another metastatic tumor diagnosis.

• - Known or expected hypersensitivity to 177Lu-DOTA-TATE, 68Ga- DOTA-TATE/TOC or any of their excipients.

• - 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

Arms

Experimental: 177Lu-DOTA-TATE and olaparib

Interventions

Drug: - 177Lu-DOTA-TATE + olaparib

177Lu-DOTA-TATE in four cycles in combination with escalated doses of olaparib