PARP Inhibitor With 177Lu-DOTA-Octreotate PRRT in Patients With Neuroendocrine Tumours

This phase 1, single arm, single centre study is designed to evaluate the safety and tolerability of talazoparib in combination with 177Lu-DOTA-Octreotate in patients with metastatic NET.

Patients will receive 1 cycle of 177Lu-DOTA-Octreotate alone followed by 3 cycles of 177Lu-DOTA-Octreotate combined with 5 days of talazoparib.

Inclusion criteria

• 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

Exclusion criteria

• Surgery or radiotherapy within <3 weeks of registration. Patients must have recovered from any effects of any major surgery.
• Any prior exposure to peptide receptor radionuclide therapy (177Lu, 111In or 90Y labelled), PARPi, immunotherapy
• Uncontrolled intercurrent illness that is likely to impede participation and /or compliance
• Other malignancies unless curatively treated with no evidence of disease within previous 3-years other than adequately treated non-melanoma skin cancer or melanoma in situ.
• Previous or current history of myelodysplastic syndrome/acute myeloid leukemia
• Patients unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with the absorption of the study medication.
• Use of strong P-gp inhibitors (eg, dronedarone, quinidine, ranolazine, verapamil, ketoconazole, itraconazole), P-gp inducers (eg, rifampin, tipranavir/ritonavir), or BCRP inhibitors (eg, elacridar [GF120918]) should be avoided.
• Participation in another clinical study with an investigational product or another systemic therapy administered in the last 3 weeks (except short acting SSA).