Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

Launched by ERASMUS MEDICAL CENTER · May 19, 2023

Keywords

ClinConnect Summary

This clinical trial is looking at a new way to improve treatment for patients with advanced neuroendocrine tumors, specifically those who have had some treatment but their disease has continued to progress. The study is testing a medication called olaparib, which is a type of drug that helps to repair damaged cells, when combined with Peptide Receptor Radionuclide Therapy (PRRT). The main goal is to find out the highest dose of olaparib that patients can safely take when given alongside PRRT. Researchers will also look at how well this combination works and if there are any specific markers in the body that could indicate a good response to the treatment.

To participate in this study, patients need to be at least 18 years old and have been diagnosed with a specific type of neuroendocrine tumor that is still progressing after initial treatment. They should also have measurable disease on imaging tests and good overall health to handle the treatment. Participants can expect to receive two cycles of PRRT along with the olaparib, and they will be closely monitored throughout the study. It's important to know that patients with certain health issues or those who have recently undergone specific treatments may not be eligible for the trial. If you're considering participating, you'll be fully informed about what to expect and will need to give consent to take part.

Gender

ALL

Eligibility criteria

• 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.