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).
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
During 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
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
RECRUITINGMaximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate
Time frame: Through study completion, up to 18 months following first administration of PRRT.
Dose limiting toxicity talazoparib
The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.
Time frame: Each cohort of 3 patients be assessed for DLTs in the first 6 weeks (cycle 2) of treatment and a dose for the next cohort will be determined (each cycle is 8 weeks)
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
Time frame: Through Study completion, up to 18 months after the last patient commences treatment.
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.
Time frame: Through study completion, up to 18 months following first administration of PRRT.
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.
Time frame: Through study completion, up to 18 months following first administration of PRRT.
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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.
Time frame: Through study completion, up to 18 months following first administration of PRRT.
Rate of Treatment discontinuation due to toxicity
The percentage of patients who discontinue treatment due to treatment related toxicity will be reported and will be also categorised by dose level
Time frame: Through study completion, up to 18 months following first administration of PRRT.