Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer
This phase II trial studies how well temozolomide with or without veliparib works in treating patients with relapsed or refractory small cell lung cancer. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving temozolomide with veliparib may be an effective treatment for relapsed or refractory small cell lung cancer.
Recurrent Small Cell Lung Cancer
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||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|
- Progression-free survival, calculated as the proportion of patients alive and without evidence of disease [ Time Frame: From randomization to time of progression or death, whichever occurs first, assessed at 4 months ] [ Designated as safety issue: No ]Compared across the two arms using a Fisher exact test.
- ORR by RECIST 1.1 criteria [ Time Frame: Assessed up to 5 years ] [ Designated as safety issue: No ]Corresponding exact two-sided 95% confidence intervals will be calculated and reported in both arms of the study. Comparisons between treatment arms will be performed using Fisher -exact test.
- Overall survival [ Time Frame: From randomization to time of death, assessed up to 5 years ] [ Designated as safety issue: No ]Estimated in each treatment group using Kaplan-Meier method. Group comparisons will be performed using log-rank test.
- Incidence of adverse events [ Time Frame: Assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Collected and tabulated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Summarized using descriptive statistics.
- Biomarker expression [ Time Frame: Baseline to up to 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||June 2012|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Arm I (veliparib and temozolomide)
Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
Other Name: ABT-888Drug: temozolomide
Other Names:Other: laboratory biomarker analysis
Active Comparator: Arm II (placebo and temozolomide)
Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
Other Names:Other: placebo
Other Name: PLCBOther: laboratory biomarker analysis
Hide Detailed Description
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.
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.
IV. Determine the safety and tolerability of ABT-888 and temozolomide in patients with SCLC.
I. Evaluate available tumor samples for methylated O6-methylguanine-deoxyribonucleic acid (DNA) methyltransferase (MGMT) promoter by the EpiTyper assay, as well as MGMT expression by immunohistochemistry and determine if these correlate with PFS, ORR, and OS.
II. Evaluate available tumor samples for poly (ADP ribose) polymerase (PARP)-1, breast cancer 1 (BRCA-1) and RAD51 expression by immunohistochemistry and determine if they correlate with PFS, ORR, and OS.
III. Evaluate available tumor samples for messenger ribonucleic acid (mRNA) BRCA-1 expression and determine if it correlates PFS, ORR, and OS.
IV. Evaluate available tumor samples for phosphatase and tensin homolog (PTEN) expression by immunohistochemistry and determine if it correlates PFS, ORR, and OS.
V. Identify and enumerate circulating tumor cells (CTCs) using the Cell Search System in these patients with SCLC at baseline and at the time of repeat imaging.
VI. Correlate the number of CTCs with PFS and OS at each time point. VII. Correlate the change in CTCs with radiographic response. VIII. Correlate the number of CTCs at baseline with patient characteristics (disease burden, location of metastases, progression at existing sites or new sites of disease).
IX. Evaluate gamma gamma H2A histone family, member X (H2AX)-positive CTCs using the CellSearch.
X. Assess the percentage increase in DNA fragments during treatment and correlate with outcome in each of the treatment groups.
XI. Evaluate plasma markers for apoptosis and angiogenesis. XII. Assess changes in plasma markers for apoptosis and angiogenesis, including M30, M65, pro-gastrin-releasing peptide (pro-GRP), soluble vascular endothelial growth factor (sVEGF), sVEGF receptor 2 (sVEGFR2), and sKIT, and correlate these markers with outcome in the two treatment arms.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7 and temozolomide PO on days 1-5.
ARM II: Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 8-12 weeks.
|United States, Maryland|
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21231|
|Contact: Christine L. Hann 410-502-0678 firstname.lastname@example.org|
|Principal Investigator: Christine L. Hann|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Ramaswamy Govindan 314-362-5737 rgovinda@DOM.wustl.edu|
|Principal Investigator: Ramaswamy Govindan|
|United States, New York|
|Memorial Sloan-Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Maria C. Pietanza 646-888-4203 email@example.com|
|Principal Investigator: Maria C. Pietanza|
|United States, Ohio|
|Case Western Reserve University||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Afshin Dowlati 216-844-5181 firstname.lastname@example.org|
|Principal Investigator: Afshin Dowlati|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Lauren A. Byers 713-792-6363 email@example.com|
|Principal Investigator: Lauren A. Byers|
|Principal Investigator:||Maria Pietanza||Memorial Sloan-Kettering Cancer Center|