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
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.
Single group
Talazoparib
DrugDuring dose escalation, doses of talazoparib that can be administered are 0.1mg, 0.25mg, 0.5mg or 1mg oral daily. Talazoparib will be given on days 2-6 of each cycle of 177Lu-DOTA-Octreotate for cycles 2-4, every 8 weeks
Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate
Dose limiting toxicity talazoparib
The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.
Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Safety of the combination will be measured by AEs and SAEs
Radiographic progression free survival
The time from treatment initiation to the first date of progression on imaging or death due to any cause. Imaging progression will be assessed by RECIST 1.1. Patients who commence new systemic therapy before evidence of disease progression on conventional imaging will be considered to have progressed.
Overall Survival
The time from treatment initiation to the date of death due to any cause. For patients alive, the time will be censored at the last time the patients was known to be alive.
Treatment discontinuation due to toxicity
The number of patients who discontinue treatment at any time due to treatment related toxicity will be reported and will be also categorised by dose level.
Click on the lead sponsor to view all of their trials.
