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

Official title

Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor

Overview

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).

Detailed description

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.

Interventions

• Drug Talazoparib
  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

Primary outcome measures

• Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate [Time frame: Through study completion, up to 18 months following first administration of PRRT.]
• Dose limiting toxicity talazoparib [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)]

Secondary outcome measures (5)

• Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [Time frame: Through Study completion, up to 18 months after the last patient commences treatment.]
• Radiographic progression free survival [Time frame: Through study completion, up to 18 months following first administration of PRRT.]
• Overall Survival [Time frame: Through study completion, up to 18 months following first administration of PRRT.]
• Treatment discontinuation due to toxicity [Time frame: Through study completion, up to 18 months following first administration of PRRT.]
• Rate of Treatment discontinuation due to toxicity [Time frame: Through study completion, up to 18 months following first administration of PRRT.]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 1 center

• Peter MacCallum Cancer Centre — Melbourne

Identifiers

NCT: NCT05053854 · PMC67199

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗