Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

Inclusion Criteria:

* Histologically proven locally advanced or metastatic, well-differentiated (grade 1, 2 or 3) NET.
* Disease progression based on RECIST v1.1 following initial or salvage treatment with PRRT with 177Lu-DOTATATE with a progression free interval of at least 12 months since first cycle of previous administration of PRRT or with no suitable systemic alternative treatment options.
* The patient is eligible for two cycles of salvage PRRT.
* Measurable disease according to RECIST v1.1 on CT/MRI.
* Confirmed presence of somatostatin receptors on all target lesions on CT/MRI, based on positive uptake on a 68Ga-DOTATATE/-TOC/-NOC PET-CT/MRI scan.
* Age ≥ 18 years.
* Karnofsky Performance Score (KPS) \> 60.

Exclusion Criteria:

* Hb concentration \<6.2 mmol/L; white blood cell count \<3x109/L; platelets \<100x109/L; neutrophil count \<1.5x109/L.
* Renal insufficiency defined as a creatinine clearance \<50 mL/min, measured in 24-hour urine collection.
* Liver function or enzyme abnormalities defined as a total bilirubin \>3 x ULN, Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 x ULN or serum albumin \<3.0 g/dL unless prothrombin time is within the normal range.
* Pregnancy, lactation and inability to comply with effective means of contraception in females of child-bearing age.
* Neuroendocrine carcinoma of any origin.
* Any surgery, radioembolization, chemoembolization, chemotherapy and radiofrequency ablation within 12 weeks prior to inclusion in the study. Interferons, everolimus, sunitinib or other systemic therapies within 4 weeks prior to inclusion in the study.
* Uncontrolled congestive heart failure (NYHA II, III, IV).
* Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
* Prior external beam radiation therapy to more than 25% of the bone marrow.
* 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.
* Patients who use a strong CYP3A4 inhibitor within 1 week before start of the treatment or a CYP3A4 inducer within 4 weeks before start of the treatment.
* History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
* Known allergy or intolerance for the (non-)investigational drugs.
* Inability to provide informed consent.
* End of life care.