NCT02537561撤回1 期
A Phase I Adaptive Design Trial of Talazoparib in Combination With Gemcitabine and Cisplatin in Patients With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
研究概览
简要总结
In this proposed study the investigators will combine gemcitabine and cisplatin with talazoparib to determine the recommended Phase 2 dose (RP2D) of this combination regimen. After determination of the RP2D patients with lung cancer whose tumors carry molecular alterations in DNA repair pathway genes will be enrolled to an expansion cohort to determine anti-tumor efficacy. Tissue samples of patients with confirmed partial response, complete response, and non-responders will be obtained for whole exome, and transcriptome sequencing to characterize the genetic alterations associated with response to therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed diagnosis of advanced solid tumor for which no curative standard treatment options exist and for which gemcitabine and cisplatin is a suitable treatment regimen.
- •After the determination of the maximum tolerated dose, an expansion cohort of 20 patients with non-small cell lung cancer whose tumors demonstrate variants in DNA repair pathway genes will be enrolled.
- •Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- •Prior treatment for this disease is allowed if it has been completed at least 2 weeks prior to study enrollment and if all treatment-related toxicities are resolved. Prior exposure to a PARP inhibitor is allowed for patients in the dose-finding portion of the study.
- •At least 18 years of age.
- •ECOG performance status ≤ 1
- •Normal bone marrow and organ function as defined below:
- •Leukocytes ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcl
- •Platelets ≥ 100,000/mcl
- •Total bilirubin ≤ 1.5 x IULN
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- •Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Tissue available for sequencing (either archival tissue or readily accessible tumor for fresh routine biopsy).
- •Able to swallow tablets.
- •Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •A history of other malignancy ≤ 5 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix.
- •Received any other investigational agent within 2 weeks of starting the first dose on study.
- •Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and previously treated. Patients must be at least 4 weeks post-brain radiation therapy.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, gemcitabine, talazoparib, or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active coronary artery disease, uncontrolled seizure, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- •Known HIV-positivity.
研究组 & 干预措施
Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors
Experimental
- Dose levels of the drugs will be dependent on which dose level the participants is enrolled.
- Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
- Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
- Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
- Cisplatin and gemcitabine will be given for a total of 6 cycles.
- Talazoparib may be continued as a single agent maintenance therapy.
干预措施: Cisplatin (Drug)
Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors
Experimental
- Dose levels of the drugs will be dependent on which dose level the participants is enrolled.
- Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
- Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
- Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
- Cisplatin and gemcitabine will be given for a total of 6 cycles.
- Talazoparib may be continued as a single agent maintenance therapy.
干预措施: Gemcitabine (Drug)
Arm 1: Cisplatin, Gemcitabine, Talazoparib Solid Tumors
Experimental
- Dose levels of the drugs will be dependent on which dose level the participants is enrolled.
- Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
- Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
- Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
- Cisplatin and gemcitabine will be given for a total of 6 cycles.
- Talazoparib may be continued as a single agent maintenance therapy.
干预措施: Talazoparib (Drug)
Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC
Experimental
- Dose levels of the drugs will depend on what the MTD is in the dose escalation portion of the study
- Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
- Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
- Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
- Cisplatin and gemcitabine will be given for a total of 6 cycles.
- Talazoparib may be continued as a single agent maintenance therapy.
干预措施: Cisplatin (Drug)
Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC
Experimental
- Dose levels of the drugs will depend on what the MTD is in the dose escalation portion of the study
- Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
- Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
- Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
- Cisplatin and gemcitabine will be given for a total of 6 cycles.
- Talazoparib may be continued as a single agent maintenance therapy.
干预措施: Gemcitabine (Drug)
Arm 2: Cisplatin, Gemcitabine, Talazoparib NSCLC
Experimental
- Dose levels of the drugs will depend on what the MTD is in the dose escalation portion of the study
- Cisplatin will be infused as a 30 minute intravenous piggyback (IVPB) on Day 1 of each 21 day cycle.
- Gemcitabine will be infused as a 30 minute IVPB on Days 1 and 8 of each 21 day cycle. On day 1, gemcitabine will be given before cisplatin.
- Talazoparib will be started with cycle 2. It is an oral drug which will be administered on an outpatient basis daily.
- Cisplatin and gemcitabine will be given for a total of 6 cycles.
- Talazoparib may be continued as a single agent maintenance therapy.
干预措施: Talazoparib (Drug)
结局指标
主要结局
Safety and toxicities as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
时间窗: 30 days after completion of treatment (estimated average to be 7 months)
Maximum tolerated dose (MTD)
时间窗: Completion of dose escalation portion of study (approximately 12 months)
The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 30% of patients in a cohort are expected to experience a dose-limiting toxicity (DLT) during the second cycle based on the CRM algorithm. Dose escalations will proceed until the MTD is determined.
Objective response rate (ORR) in preselected patients with BRCAness tumoral genotype
时间窗: Up to completion of treatment (estimated average of 6 months)
ORR - proportion of patients who achieved a complete response or a partial response
次要结局
- Disease control rate (DCR)(Until death (estimated average to be 12 months))
- Progression-free survival (PFS)(Until death (estimated average to be 12 months))
- Objective response rate (ORR)(Up to completion of treatment (estimated average of 6 months))
- Overall survival (OS)(Until death (estimated average to be 12 months))
研究者
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