Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer
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
9 other identifiers
interventional
97
1 country
14
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2012
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 9, 2012
CompletedFirst Posted
Study publicly available on registry
July 11, 2012
CompletedStudy Start
First participant enrolled
July 27, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 9, 2017
CompletedResults Posted
Study results publicly available
March 27, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
March 25, 2027
ExpectedApril 29, 2026
March 1, 2026
4.5 years
July 9, 2012
February 27, 2018
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease
Compared across the two arms using a Fisher exact test.
From randomization to time of progression or death, whichever occurs first, assessed at 4 months
Secondary Outcomes (3)
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
Overall Survival
From randomization to time of death
Number of Participants With Adverse Events
From the start of treatment until 30 days from coming off treatment
Other Outcomes (9)
BRCA1 Expression, Assessed by Immunohistochemistry
Up to 5 years
Changes in Plasma Markers
Baseline to up to 5 years
GammaH2AX Levels
Up to 5 years
- +6 more other outcomes
Study Arms (2)
Arm I (veliparib and temozolomide)
EXPERIMENTALPatients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
Arm II (placebo and temozolomide)
ACTIVE COMPARATORPatients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
Interventions
Correlative studies
Given PO
Given PO
Eligibility Criteria
You may qualify if:
- 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
- +3 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, 21224, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Sleepy Hollow
Sleepy Hollow, New York, 10591, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Related Publications (1)
Pietanza MC, Waqar SN, Krug LM, Dowlati A, Hann CL, Chiappori A, Owonikoko TK, Woo KM, Cardnell RJ, Fujimoto J, Long L, Diao L, Wang J, Bensman Y, Hurtado B, de Groot P, Sulman EP, Wistuba II, Chen A, Fleisher M, Heymach JV, Kris MG, Rudin CM, Byers LA. Randomized, Double-Blind, Phase II Study of Temozolomide in Combination With Either Veliparib or Placebo in Patients With Relapsed-Sensitive or Refractory Small-Cell Lung Cancer. J Clin Oncol. 2018 Aug 10;36(23):2386-2394. doi: 10.1200/JCO.2018.77.7672. Epub 2018 Jun 15.
PMID: 29906251DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Charles Rudin
- Organization
- Memorial Sloan Kettering Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Charles M Rudin
Memorial Sloan Kettering Cancer Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 9, 2012
First Posted
July 11, 2012
Study Start
July 27, 2012
Primary Completion
January 9, 2017
Study Completion (Estimated)
March 25, 2027
Last Updated
April 29, 2026
Results First Posted
March 27, 2018
Record last verified: 2026-03