A Multi-Center, Randomized, Double-Blind Phase II Study Comparing ABT-888, a PARP Inhibitor, Versus Placebo With Temozolomide in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 97
- 试验地点
- 28
- 主要终点
- Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease
研究概览
简要总结
This randomized phase II trial studies how well temozolomide with or without veliparib works in treating patients with small cell lung cancer that has returned or does not respond to treatment. Temozolomide works by damaging molecules inside the cancer cells, such as deoxyribonucleic acid (DNA), that are needed for cancer survival and growth. Veliparib may stop the growth of tumor cells by blocking proteins that are needed for repairing the damaged DNA and it may also help temozolomide to kill more cancer cells. It is not yet know whether temozolomide is more effective with or without veliparib in treating patients with relapsed or refractory small cell lung cancer.
详细描述
PRIMARY OBJECTIVES:
I. To demonstrate an improvement in progression free survival (PFS) at four months in patients with relapsed sensitive or refractory small cell lung cancer (SCLC) receiving ABT-888 (veliparib) and temozolomide compared to placebo and temozolomide.
SECONDARY OBJECTIVES:
I. Determine the objective response rate (ORR) (based on Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) in both arms of the study: ABT-888 and temozolomide and placebo and temozolomide.
II. Determine the overall survival (OS) of patients in both arms of the study. III. Determine the ORR, PFS and OS of ABT-888 and temozolomide and placebo and temozolomide, in the following patient groups: sensitive disease vs. refractory disease; second-line treatment vs. third-line treatment; brain metastases vs. no brain metastases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Patients must have histologically or cytologically confirmed small cell lung cancer; confirmation will be done at Memorial Sloan-Kettering Cancer Center (MSKCC) or locally for participating sites
- •Patients' disease has relapsed or progressed after one or two prior chemotherapy regimens, one of which must have been an etoposide-platinum doublet; eligible patients will be defined as follows:
- •"Sensitive" disease: patients who had one previous line of chemotherapy and maintained an appropriate response for > 60 days
- •"Refractory" disease: those patients with either (a) no response to first-line chemotherapy or progression =< 60 days after completing treatment, or (b) "sensitive" or "refractory" disease in need of third-line therapy (i.e. completed or failed two previous lines of chemotherapy)
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
- •Patients with asymptomatic brain metastases that do not require immediate whole brain radiation therapy and are on stable doses of steroids are allowed
- •Patients must have measurable disease, which is defined as at least one lesion that can be accurately measured in at least one dimension on a computed tomography (CT) scan as per RECIST version 1.1; brain metastases can be considered measurable disease if they meet this criterion
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Hemoglobin >= 8.5 g/dL; the use of transfusion to achieve this criterion should be at the discretion of the investigators
- •Total bilirubin =< 1.5 mg/dL x institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional upper limit of normal
- •Creatinine =< 1.5 x institutional upper limit of normal OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels >= 1.5 x upper limit of institutional normal
- •Women of child-bearing 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 should inform her treating physician immediately
- •For women of child-bearing potential, negative pregnancy test within 14 days prior to starting temozolomide and ABT-888
- •Ability to understand and the willingness to sign a written informed consent document
- •Able to swallow pills
- •Patients will not be excluded based on the diagnosis of acquired immune deficiency syndrome (AIDS); given the increased risk of infection, these patients should have cluster of differentiation (CD)4 counts above 200 cells/mm^3; patients with AIDS or human immunodeficiency virus (HIV) not receiving agents with the potential for pharmacokinetic interactions with ABT-888 may be eligible
排除标准
- •Patients who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study
- •Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier; toxicities should have resolved to baseline or to within one grade level of their baseline (not to exceed grade 2)
- •Patients who have been administered ABT-888, any other PARP-inhibitor, or temozolomide
- •Patients may not be receiving any other investigational agents
- •Patients with leptomeningeal involvement
- •Patients with active seizures or a history of seizures
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or temozolomide
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with ABT-888; these potential risks also apply to temozolomide
- •Patients with either AIDS or HIV on combination antiretroviral therapy are ineligible
- •Patients with a synchronous active malignancy requiring treatment
研究组 & 干预措施
Arm I (veliparib and temozolomide)
Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo and temozolomide)
Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
干预措施: Placebo Administration (Other)
Arm II (placebo and temozolomide)
Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (veliparib and temozolomide)
Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
干预措施: Temozolomide (Drug)
Arm I (veliparib and temozolomide)
Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
干预措施: Veliparib (Drug)
Arm II (placebo and temozolomide)
Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease
时间窗: From randomization to time of progression or death, whichever occurs first, assessed at 4 months
Compared across the two arms using a Fisher exact test.
次要结局
- Overall Survival(From randomization to time of death)
- Overall Response (ORR) by RECIST 1.1 Criteria(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months)
- Number of Participants With Adverse Events(From the start of treatment until 30 days from coming off treatment)