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Recurrent Lung Small Cell CarcinomaPhase 2NCT01638546

Temozolomide With or Without Veliparib in Treating Patients With Relapsed or Refractory Small Cell Lung Cancer

A Phase 2 study testing Laboratory Biomarker Analysis, Temozolomide and Veliparib in people with Recurrent Lung Small Cell Carcinoma, run by National Cancer Institute (NCI) at 14 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Lung Small Cell Carcinoma
What is being tested?
Laboratory Biomarker Analysis, Temozolomide and Veliparib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
97 participants
Where
14 sitesUnited States
Study dates
27 Jul 2012to 25 Mar 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland, 21224

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • Memorial Sloan Kettering Sleepy Hollow

    Sleepy Hollow, New York, 10591

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

TERTIARY OBJECTIVES:

  1. Evaluate available tumor samples for methylated O6-methylguanine-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 recombinase (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.

  1. 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 H2A histone family, member X (H2AX)-positive CTCs using the CellSearch.

  1. 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 caspase-cleaved cytokeratin 18 fragment (M30), soluble cytokeratin 18 (M65), pro-gastrin-releasing peptide (pro-GRP), soluble vascular endothelial growth factor (sVEGF), sVEGF receptor 2 (sVEGFR2), and soluble v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (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.

Being tested
Laboratory Biomarker Analysis, Placebo Administration, Temozolomide, Veliparib
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Placebo AdministrationOther

    Given PO

  • TemozolomideDrug

    Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831

    Given PO

  • VeliparibDrug

    Also called ABT 888, ABT-888, ABT888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT01638546
Study groupRoleWhat they receive
Arm I (veliparib and temozolomide)ExperimentalPatients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
Receives: Other: Laboratory Biomarker Analysis; Drug: Temozolomide; Drug: Veliparib
Arm II (placebo and temozolomide)Active comparatorPatients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Drug: Temozolomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: From randomization to time of progression or death, whichever occurs first, assessed at 4 months

Secondary outcomes (3)

  1. Overall Response (ORR) by RECIST 1.1 Criteria

    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.

    Measured: 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

  2. Overall Survival

    Estimated in each treatment group using Kaplan-Meier method. Group comparisons will be performed using log-rank test.

    Measured: From randomization to time of death

  3. Number of Participants With Adverse Events

    Tabulated According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Summary level.

    Measured: From the start of treatment until 30 days from coming off treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2012 (estimated)
  2. Study start27 Jul 2012
  3. Primary completion9 Jan 2017
  4. Study completion25 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01638546
Sponsor's protocol ID
NCI-2012-01130
Other IDs
NCI-2012-01130, CDR0000737062, 12-021, IRB #12-021, 9026, 9026, N01CM00039, P30CA008748
Status last verified
Sep 2026
First submitted
9 Jul 2012
Last updated
30 Sep 2026
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29906251

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Temozolomide and Veliparib in people with Recurrent Lung Small Cell Carcinoma, run by National Cancer Institute (NCI) at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01638546, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.

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