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Témozolomide avec ou sans véliparib dans le traitement des patients atteints d'un cancer du poumon à petites cellules en rechute ou réfractaire

11 novembre 2026 mis à jour par: National Cancer Institute (NCI)

Une étude de phase II multicentrique, randomisée et en double aveugle comparant l'ABT-888, un inhibiteur de la PARP, à un placebo avec le témozolomide chez des patients atteints d'un cancer du poumon à petites cellules sensible ou réfractaire en rechute

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.

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Intervention / Traitement

Description détaillée

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.

IV. Determine the safety and tolerability of ABT-888 and temozolomide in patients with SCLC.

TERTIARY OBJECTIVES:

I. 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.

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 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 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.

Type d'étude

Interventionnel

Inscription (Réel)

97

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Florida
      • Tampa, Florida, États-Unis, 33612
        • Moffitt Cancer Center
    • Georgia
      • Atlanta, Georgia, États-Unis, 30322
        • Emory University Hospital/Winship Cancer Institute
    • Maryland
      • Baltimore, Maryland, États-Unis, 21287
        • Johns Hopkins University/Sidney Kimmel Cancer Center
      • Baltimore, Maryland, États-Unis, 21224
        • Johns Hopkins Bayview Medical Center
    • Missouri
      • St Louis, Missouri, États-Unis, 63110
        • Washington University School of Medicine
    • New Jersey
      • Basking Ridge, New Jersey, États-Unis, 07920
        • Memorial Sloan Kettering Basking Ridge
    • New York
      • Commack, New York, États-Unis, 11725
        • Memorial Sloan Kettering Commack
      • New York, New York, États-Unis, 10065
        • Memorial Sloan Kettering Cancer Center
      • Sleepy Hollow, New York, États-Unis, 10591
        • Memorial Sloan Kettering Sleepy Hollow
      • Uniondale, New York, États-Unis, 11553
        • Memorial Sloan Kettering Nassau
    • North Carolina
      • Chapel Hill, North Carolina, États-Unis, 27599
        • UNC Lineberger Comprehensive Cancer Center
    • Ohio
      • Cleveland, Ohio, États-Unis, 44106
        • Case Western Reserve University
    • Texas
      • Houston, Texas, États-Unis, 77030
        • UT MD Anderson Cancer Center
    • Virginia
      • Richmond, Virginia, États-Unis, 23298
        • VCU Massey Comprehensive Cancer Center

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Arm I (veliparib and temozolomide)

Patients receive veliparib PO BID on days 1-7 and temozolomide PO on days 1-5.
Autre: Laboratory Biomarker Analysis

Correlative studies

Médicament: Temozolomide

Given PO

Autres noms:
  • Témodar
  • SCH 52365
  • Temodal
  • Temcad
  • Méthazolastone
  • RP-46161
  • Temomedac
  • TMZ
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tétrazine-8-carboxamide, 3, 4-dihydro-3-méthyl-4-oxo-
  • M&B 39831
  • M et B 39831
  • Gliotème
  • Témizole
Médicament: Veliparib

Given PO

Autres noms:
  • ABT-888
  • Inhibiteur PARP-1 ABT-888
  • ABT888
Comparateur actif: Arm II (placebo and temozolomide)

Patients receive placebo PO BID on days 1-7 and temozolomide as in Arm I.
Autre: Laboratory Biomarker Analysis

Correlative studies

Autre: Placebo Administration

Given PO

Médicament: Temozolomide

Given PO

Autres noms:
  • Témodar
  • SCH 52365
  • Temodal
  • Temcad
  • Méthazolastone
  • RP-46161
  • Temomedac
  • TMZ
  • CCRG-81045
  • Imidazo[5,1-d]-1,2,3,5-tétrazine-8-carboxamide, 3, 4-dihydro-3-méthyl-4-oxo-
  • M&B 39831
  • M et B 39831
  • Gliotème
  • Témizole

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease
Délai: 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.
From randomization to time of progression or death, whichever occurs first, assessed at 4 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall Response (ORR) by RECIST 1.1 Criteria
Délai: 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

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.
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
Délai: From randomization to time of death

Estimated in each treatment group using Kaplan-Meier method. Group comparisons will be performed using log-rank test.
From randomization to time of death
Number of Participants With Adverse Events
Délai: From the start of treatment until 30 days from coming off treatment

Tabulated According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Summary level.
From the start of treatment until 30 days from coming off treatment

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
BRCA1 Expression, Assessed by Immunohistochemistry
Délai: Up to 5 years

Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Up to 5 years
Changes in Plasma Markers
Délai: Baseline to up to 5 years

Correlated with outcome in the two treatment arms.
Baseline to up to 5 years
GammaH2AX Levels
Délai: Up to 5 years

Wilcoxon test will be used to compare the percentage increase of gammaH2AX positive cells between the two treatment groups.
Up to 5 years
MGMT Expression, Assessed by Immunohistochemistry
Délai: Up to 5 years

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.
Up to 5 years
Number of Circulating Tumor Cells
Délai: Up to 5 years

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.
Up to 5 years
PARP-1 Expression
Délai: Up to 5 years

Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Up to 5 years
Presence of MGMT Promoter Methylation, Assessed by the EpiTyper Assay
Délai: Up to 5 years

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.
Up to 5 years
PTEN Expression, Assessed by Immunohistochemistry
Délai: Up to 5 years

Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Up to 5 years
RAD51 Expression, Assessed by Immunohistochemistry
Délai: Up to 5 years

Fisher's exact test will be used to correlate response and log-rank test to correlate with progression free survival and overall survival.
Up to 5 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

National Cancer Institute (NCI)

Les enquêteurs

  • Chercheur principal: Charles M Rudin, Memorial Sloan Kettering Cancer Center

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

27 juillet 2012

Achèvement primaire (Réel)

9 janvier 2017

Achèvement de l'étude (Estimé)

25 mars 2027

Dates d'inscription aux études

Première soumission

9 juillet 2012

Première soumission répondant aux critères de contrôle qualité

9 juillet 2012

Première publication (Estimé)

11 juillet 2012

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

13 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

11 novembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • NCI-2012-01130
  • U01CA070095 (Subvention/contrat des NIH des États-Unis)
  • UM1CA186691 (Subvention/contrat des NIH des États-Unis)
  • P30CA008748 (Subvention/contrat des NIH des États-Unis)
  • N01CM00039 (Subvention/contrat des NIH des États-Unis)
  • 9026 (Autre identifiant: CTEP)
  • NCI-2012-01130 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
  • IRB #12-021
  • 12-021
  • CDR0000737062
  • 9026 (Autre identifiant: Memorial Sloan Kettering Cancer Center)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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