well-differentiated advanced gastroenteropancreatic neuro-endocrine tumors.
Conditions
Interventions
Olaparib (18 days) during 2 PRRT cycles.
Sponsors
Erasmus MC, Rotterdam, the Netherland
Eligibility
Inclusion criteria
Inclusion criteria: - Histologically proven locally advanced or metastatic, well-differentiated 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 - Two cycles of PRRT are considered by the treating physician - 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
Exclusion criteria: - Hb concentration 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose (MTD) of olaparib in combination with PRRT in patients with a well-differentiated advanced NET, progressive after treatment with PRRT. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy, pharmacokinetics (PK) and biomarker response of olaparib in combination with PRRT in patients with a well-differentiated advanced NET, progressive after treatment with PRRT. | — |
Contacts
Public ContactNina Becx
Erasmus MC
Outcome results
None listed