Testing olaparib with radiation therapy for advanced neuroendocrine tumors

Trial details

Who runs it

Erasmus Medical Center

Trial code

NCT05870423

Record updated

5 June 2025

Original description

This is a phase 1 dose-escalation study to determine the maximum tolerated dose of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced gastroenteropancreatic NET (GEP NET), progressive after PRRT. As secondary objectives, efficacy, pharmacokinetics and biomarker response will be investigated.Read full original descriptionShow less

Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

This is a phase 1 dose-escalation study to determine the maximum tolerated dose of the PARP inhibitor olaparib in combination with PRRT in patients with a well-differentiated advanced gastroenteropancreatic NET (GEP NET), progressive after PRRT. As secondary objectives, efficacy, pharmacokinetics and biomarker response will be investigated.

Inclusion: 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: 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; Prior external beam radiation therapy to more than 25% of the bone marrow; 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; Known allergy or intolerance for the (non-)investigational drugs; 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; 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; 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; 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; Inability to provide informed consent; End of life care.

ClinicalTrials.gov NCT05870423