Improving Peptide Receptor Radionuclide Therapy With PARP Inhibitors

• Status: Recruiting
• Trial end date: 2025-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasmus Medical Center
• Treatments: Olaparib

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.