Phase 1 Trial of PARP Inhibitor Combined With 177Lu-DOTA-Octreotate Peptide Receptor Radionuclide Therapy (PRRT) in Patients With Metastatic NeuroEndocrine Tumor
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
177Lu-DOTA-Octreotate + talazoparib
Patients will receive 4 cycles of 177Lu-DOTA-Octreotate every 8 weeks, the last 3 cycles combined with talazoparib on days 2-6 of each cycle.
干预措施: Talazoparib (Drug)
结局指标
主要结局
Maximum tolerated dose Talazoparib with 177Lu-DOTA-Octreotate
时间窗: Through study completion, up to 18 months following first administration of PRRT.
Maximum tolerated dose of Talazoparib when given in combination with 177Lu-DOTA-Octreotate
Dose limiting toxicity talazoparib
时间窗: 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)
The toxicity (haematologic or non-haematologic) that prevents further administration of the trial talazoparib treatment at that dose level.
次要结局
- Overall Survival(Through study completion, up to 18 months following first administration of PRRT.)
- Adverse Events and Serious Adverse Events measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0(Through Study completion, up to 18 months after the last patient commences treatment.)
- Radiographic progression free survival(Through study completion, up to 18 months following first administration of PRRT.)
- Treatment discontinuation due to toxicity(Through study completion, up to 18 months following first administration of PRRT.)
- Rate of Treatment discontinuation due to toxicity(Through study completion, up to 18 months following first administration of PRRT.)