A Phase I Study of Talazoparib and Consolidative Thoracic Radiotherapy for Extensive Stage Small Cell Lung Cancer
概览
- 阶段
- 1 期
- 干预措施
- Talazoparib in Combination with Low Dose Radiotherapy (RT)
- 疾病 / 适应症
- Lung Cancer
- 发起方
- University Health Network, Toronto
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
This is a phase I, dose escalating study evaluating the safety of combining talazoparib and low dose consolidative thoracic radiotherapy for small cell lung cancer patients. This study will also determine the maximum tolerated dose (MTD) of talazoparib in combination with low dose thoracic radiotherapy.
Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of radiation therapy. Up to 24 patients will be enrolled to the study, where the first 3 patients will start with a starting dose level of talazoparib is 0.5 mg PO once daily. This will increase to 1mg daily with each new cohort.
详细描述
This is a phase I, dose escalating study evaluating the safety of combination talazoparib and low dose consolidative thoracic radiotherapy for extensive-stage small cell lung cancer patients with at least stable disease after standard of care 4 - 6 cycles of chemotherapy (a platinum agent and etoposide). This study will also determine the maximum tolerated dose (MTD) of talazoparib in combination with low dose thoracic radiotherapy. Secondary objectives will be to examine clinical outcomes, including locoregional recurrence within the radiation field, progression-free survival, overall survival and acute/chronic toxicities up to 1 year. Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT. Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Up to 24 patients will be enrolled to the study, where the first 3 patients will start with a starting dose level of talazoparib is 0.5 mg PO once daily. This will increase to 1mg daily with each new cohort. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.
研究者
入排标准
入选标准
- •Histological documented diagnosis of SCLC confirmed by a UHN pathologist.
- •Documented extensive disease
- •Completion of induction chemotherapy, 4-6 cycles of a platinum agent and etoposide.
- •No disease progression (i.e.SD or better response by RECIST 1.1) at the completion of chemotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnosfsky Performance Score (KPS) ≥50; see Appendix B).
- •Adequate organ and marrow function,
- •Postmenopausal or evidence of non-childbearing status for women of childbearing potential negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
排除标准
- •Untreated brain metastases.
- •Previous radiotherapy to thorax (prior breast RT is permitted).
- •Patients receiving any systemic chemotherapy, radiotherapy or immunotherapy (except for standard of care treatments or palliative reasons) within 3 weeks prior to study treatment.
- •Exposure to an investigational product within 30 days or 5 half-lives (whichever is longer) prior to start of the current study drug.
- •Any previous treatment with PARP inhibitor, including talazoparib.
- •Concomitant use of strong P-gp inhibitors
- •Concomitant use of other known P-gp inhibitors, P-gp inducers, or BCRP inhibitors
- •Persistent toxicities (\>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia.
- •Patients with myelodysplastic syndrome/acute leukaemia or with features suggestive thereof.
- •Major surgery within 2 weeks of study treatment initiation and patients must have recovered from any effects of any major surgery.
研究组 & 干预措施
Talazoparib in Combination with Low Dose RT
Patients will start on talazoparib on day 1 of study intervention, and will continue to orally take talazoparib until the last day of RT (until day 20-23). Patient will start low dose RT on day 6-9, and will continue for 10 fractions throughout 2 weeks. Talazoparib dose levels will start at 0.5mg daily and increase to 1mg if dose limiting toxicites are not observed. Toxicities include renal impairment and other treatment related toxicities Grade ≥3. Patients will be monitored weekly during study treatment, and followed up at 3 weeks, and every 3 months after for 1 year.
干预措施: Talazoparib in Combination with Low Dose Radiotherapy (RT)
结局指标
主要结局
Safety of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
时间窗: Up to 3 years upon enrollment
Safety will be measured by assessing all adverse events as determined by the investigator using CTCAE v.5.0.
Maximum Tolerated Dose (MTD) of Talazoparib in Combination with Low Dose Thoracic Radiotherapy
时间窗: Up to 1 year
MTD will be defined as the maximum dose by a standard 3+3 design
次要结局
- Loco-regional Recurrence(6 months and 1 year)
- Overall Survival (OS)(6 months and 1 year)
- Acute Toxicities(Up to 1 year)
- Progression-Free Survival (PFS)(6 months and 1 year)
- Chronic Toxicities(Up to 1 year)