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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

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

Вторичные конечные точки (5)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Peter MacCallum Cancer Centre — Melbourne

Идентификаторы

NCT: NCT05053854 · PMC67199

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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