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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01638546
First received: July 9, 2012
Last updated: May 28, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Recurrent Small Cell Lung Carcinoma
Other: Laboratory Biomarker Analysis
Other: Placebo
Drug: Temozolomide
Drug: Veliparib
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • Incidence of adverse events, tabulated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Summarized using descriptive statistics.

  • 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.


Other Outcome Measures:
  • BRCA1 expression, assessed by immunohistochemistry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.

  • Changes in plasma markers [ Time Frame: Baseline to up to 5 years ] [ Designated as safety issue: No ]
    Correlated with outcome in the two treatment arms.

  • GammaH2AX levels [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Wilcoxon test will be used to compare the percentage increase of gammaH2AX positive cells between the two treatment groups.

  • MGMT expression, assessed by immunohistochemistry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Results will be expressed as binary variables. Associations with objective response, with progression free survival and with overall survival will be tested using Fisher's exact test and log-rank test, respectively.

  • Number of circulating tumor cells [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The number of CTCs will be correlated with PFS and OS using Cox proportional hazards model. The change in CTCs will be correlated with radiographic response. The number of CTCs at baseline will be correlated with patient characteristics (disease burden, location of metastases, and progression at existing sites or new sites of disease). The number of CTC will be explored as a continuous variable and the presence of a threshold predictive of the outcome will be investigated.

  • PARP-1 expression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.

  • Presence of MGMT promoter methylation, assessed by the EpiTyper assay [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Results will be expressed as binary variables. Associations with objective response, with progression free survival and with overall survival will be tested using Fisher's exact test and log-rank test, respectively.

  • PTEN expression, assessed by immunohistochemistry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.

  • RAD51 expression, assessed by immunohistochemistry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.


Estimated Enrollment: 100
Study Start Date: June 2012
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (veliparib and temozolomide)
Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Temozolomide
Given PO
Other Names:
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Methazolastone
  • RP-46161
  • SCH 52365
  • Temodal
  • Temodar
  • TEMOZOLOMIDE
Drug: Veliparib
Given PO
Other Names:
  • ABT-888
  • PARP-1 inhibitor ABT-888
  • VELIPARIB
Active Comparator: Arm II (placebo and temozolomide)
Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Placebo
Given PO
Other Names:
  • placebo
  • placebo therapy
  • PLCB
  • sham therapy
Drug: Temozolomide
Given PO
Other Names:
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-
  • M & B 39831
  • M and B 39831
  • Methazolastone
  • RP-46161
  • SCH 52365
  • Temodal
  • Temodar
  • TEMOZOLOMIDE

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01638546

Locations
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Investigators
Principal Investigator: Maria Pietanza Memorial Sloan Kettering Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01638546     History of Changes
Other Study ID Numbers: NCI-2012-01130, NCI-2012-01130, 12-021, CDR0000737062, IRB # 12-021, 9026, N01CM00039, P30CA008748, U01CA070095, UM1CA186691
Study First Received: July 9, 2012
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on July 30, 2015