Primary Outcome Measures
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: up to 6 months after last treatment cycle ]
To assess the number of participants with toxicity of 177Lu-DOTA-TATE in combination with olaparib measured by NCI Common Toxicity Criteria v 5.0
Secondary Outcome Measures
- TTP [ Time Frame: 3 years ]
Time to progression
- Response rate [ Time Frame: 12 months after last treatment cycle ]
Response rate (RECIST) at 3 and 12 months
- OS [ Time Frame: 3 years ]
Overall survival
- DOR [ Time Frame: 3 years ]
Duration of response
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
