Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor
This phase 1 dose-escalation study is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate peptide receptor radionuclide therapy (PRRT) in patients with metastatic pancreatic or midgut neuroendocrine tumour (NET).
• Patient must be \> or equal to18 years of age and must have provided written informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Histologically confirmed Grade 2 NET, Ki-67 of 3-20%, from pancreatic or intestinal origin.
• Patient clinically suitable for PRRT
• Tumor SSR uptake on GaTate PET/CT higher than liver activity, ≥ modified Krenning 3 score
• No discordant FDG-avid disease on FDG PET/CT
• No evidence of significant uncorrected carcinoid heart disease
• Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled assessments
• Patients must have adequate bone marrow, hepatic and renal function defined as:
‣ Haemoglobin ≥100 g/L
⁃ Absolute neutrophil count ≥1.5x109/L
⁃ Platelets ≥150 x109/L
⁃ Total bilirubin ≤1.5 x upper limit of normal (ULN)
⁃ Aspartate transaminase (AST) (SGOT) and alanine transaminase (ALT) (SGPT)
‣ ≤2.5 x ULN if there is no evidence of liver metastasis or ≤5 x ULN in the presence of liver metastases.
⁃ Albumin ≥ 30 g/L
⁃ Adequate renal function: eGFR ≥ 50 ml/min