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Comparison of Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Adults With Brain Metastases From Non-Small Cell Lung Cancer

Primary Purpose

Brain Metastases From Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Veliparib
Placebo
Whole brain radiation therapy
Sponsored by
AbbVie (prior sponsor, Abbott)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases From Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subject must have cytologically or histologically confirmed non-small cell lung cancer
  • Subject must have brain metastases demonstrated on a magnetic resonance imaging (MRI) brain scan.
  • Subject must be eligible for treatment with WBRT
  • Subject must have had adequate hematologic, renal, and hepatic function.

Exclusion Criteria:

  • Subject is diagnosed with brain metastases greater than 28 days prior to Day 1
  • Subject received any prior form of cranial radiation and/or neurosurgery for their brain metastases
  • Subject's last dose of anti-cancer therapy or investigational therapy was less than or equal to 7 days prior to Day 1
  • Subject has a Karnofsky Performance Score of less than 70
  • Subject has significant dyspnea requiring supplemental oxygen therapy
  • Subject has liver metastases (restaging is not required for known liver metastases)
  • Subject has more than 2 sites (organ systems) of metastases from non-small cell lung cancer with the exception of intra-cranial sites of metastases from non-small cell lung cancer, thoracic sites of metastases from non-small cell lung cancer and bone metastases
  • Subject has leptomeningeal metastases or subarachnoid spread of tumor
  • Subject has unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment
  • Subject has a known seizure disorder that is uncontrolled, or has seizures occurring greater than or equal to 3 times a week over the past month. Subjects presenting with symptoms of seizures from the brain metastases are eligible; however he/she should receive adequate anti-seizure medication prior to study treatment
  • Subject is pregnant or lactating
  • Subject has previously been treated with a poly-(ADP-ribose)-polymerase inhibitor as an investigational agent
  • Subject has clinically significant and uncontrolled major medical condition(s)
  • Subject has a history of another active cancer within the past 5 years except: cervical cancer in situ, in situ carcinoma of the bladder, basal or squamous cell carcinoma of the skin or other cancer in situ that is considered cured

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Placebo Comparator

    Arm Label

    Veliparib 200 mg BID + WBRT

    Veliparib 50 mg BID + WBRT

    Placebo BID + WBRT

    Arm Description

    Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.

    Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.

    Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.

    Outcomes

    Primary Outcome Measures

    Overall Survival
    Overall survival was defined as the number of days from the date of randomization to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study treatment or after treatment was discontinued. If a participant had not died, the data were censored at the date the participant was last known to be alive.

    Secondary Outcome Measures

    Best Tumor Response Rate
    Best tumor response rate was calculated as the percentage of participants with a complete response or partial response, as determined by brain scan imaging (magnetic resonance image or computed tomography) by a central imaging vendor. Response was assessed according to the modified bidimensional criteria: Complete response required all of the following: complete disappearance of all target and non-target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease; no systemic corticosteroid dose. Partial response required all of the following: ≥ 50% decrease compared with baseline in the size of all target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease and no unequivocal progression of non-target lesions, which, even in presence of stable disease or progressive disease in target lesions, was significant enough to qualify as progression; stable or reduced daily total systemic corticosteroid dose.
    Time to Intracranial Progression (Radiographic)
    Time to intracranial progression (radiographic) was defined as the number of days from the date of randomization to the date of the first intracranial progression, as determined by brain scan imaging (magnetic resonance image [MRI]/ computed tomography [CT] scan) by a central imaging vendor. All confirmed events of intracranial progression were included, regardless of whether the event occurred while the participant was still taking study treatment or had previously discontinued study treatment. If the participant did not have a confirmed event of intracranial progression, their data were censored at the date of the last available intracranial progression assessment. Time to intracranial progression (radiographic) was estimated for each treatment group using Kaplan-Meier methodology.
    Time to Clinical Brain Metastasis Progression
    Time to clinical brain metastases progression was defined as the number of days from randomization to the date of the first experience of clinical brain metastases progression, as assessed by a team of neuro-oncology experts (Event Review Board). All events of clinical brain metastasis progression were included, regardless of whether the event occurred while the participant was still receiving study treatment or had previously discontinued study treatment. If a participant did not have an event of clinical brain metastases progression, their data were censored at the date of the last available clinical disease progression assessment. Time to clinical brain metastasis progression was estimated for each treatment group using Kaplan-Meier methodology.

    Full Information

    First Posted
    August 2, 2012
    Last Updated
    May 2, 2018
    Sponsor
    AbbVie (prior sponsor, Abbott)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01657799
    Brief Title
    Comparison of Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Adults With Brain Metastases From Non-Small Cell Lung Cancer
    Official Title
    A Randomized, Double-Blind, Phase 2, Dose-Ranging Study to Evaluate the Safety and Efficacy of Veliparib and Whole Brain Radiation Therapy Versus Placebo and Whole Brain Radiation Therapy in Subjects With Brain Metastases From Non-Small Cell Lung Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    October 19, 2012 (undefined)
    Primary Completion Date
    January 22, 2015 (Actual)
    Study Completion Date
    January 22, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AbbVie (prior sponsor, Abbott)

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The primary objective of this study is to evaluate the efficacy and safety of veliparib and whole brain radiation therapy in adults with brain metastases from non-small cell lung cancer (NSCLC).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Brain Metastases From Non-small Cell Lung Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    307 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Veliparib 200 mg BID + WBRT
    Arm Type
    Experimental
    Arm Description
    Participants received veliparib 200 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
    Arm Title
    Veliparib 50 mg BID + WBRT
    Arm Type
    Experimental
    Arm Description
    Participants received veliparib 50 mg twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
    Arm Title
    Placebo BID + WBRT
    Arm Type
    Placebo Comparator
    Arm Description
    Participants received placebo twice a day (BID) orally concomitantly with whole brain radiation therapy (WBRT). Participants received a total of 30.0 Gy of WBRT given in 10 daily fractions of 3.0 Gy, excluding weekends and holidays.
    Intervention Type
    Drug
    Intervention Name(s)
    Veliparib
    Other Intervention Name(s)
    ABT-888
    Intervention Description
    Veliparib capsules for oral administration
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo to veliparib capsules for oral administration
    Intervention Type
    Radiation
    Intervention Name(s)
    Whole brain radiation therapy
    Intervention Description
    30.0 grays (Gy) of WBRT given in 10 daily fractions of 3.0 Gy each, excluding weekends and holidays
    Primary Outcome Measure Information:
    Title
    Overall Survival
    Description
    Overall survival was defined as the number of days from the date of randomization to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study treatment or after treatment was discontinued. If a participant had not died, the data were censored at the date the participant was last known to be alive.
    Time Frame
    From randomization up to 36 months
    Secondary Outcome Measure Information:
    Title
    Best Tumor Response Rate
    Description
    Best tumor response rate was calculated as the percentage of participants with a complete response or partial response, as determined by brain scan imaging (magnetic resonance image or computed tomography) by a central imaging vendor. Response was assessed according to the modified bidimensional criteria: Complete response required all of the following: complete disappearance of all target and non-target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease; no systemic corticosteroid dose. Partial response required all of the following: ≥ 50% decrease compared with baseline in the size of all target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease and no unequivocal progression of non-target lesions, which, even in presence of stable disease or progressive disease in target lesions, was significant enough to qualify as progression; stable or reduced daily total systemic corticosteroid dose.
    Time Frame
    From randomization up to 24 months
    Title
    Time to Intracranial Progression (Radiographic)
    Description
    Time to intracranial progression (radiographic) was defined as the number of days from the date of randomization to the date of the first intracranial progression, as determined by brain scan imaging (magnetic resonance image [MRI]/ computed tomography [CT] scan) by a central imaging vendor. All confirmed events of intracranial progression were included, regardless of whether the event occurred while the participant was still taking study treatment or had previously discontinued study treatment. If the participant did not have a confirmed event of intracranial progression, their data were censored at the date of the last available intracranial progression assessment. Time to intracranial progression (radiographic) was estimated for each treatment group using Kaplan-Meier methodology.
    Time Frame
    From randomization up to 24 months
    Title
    Time to Clinical Brain Metastasis Progression
    Description
    Time to clinical brain metastases progression was defined as the number of days from randomization to the date of the first experience of clinical brain metastases progression, as assessed by a team of neuro-oncology experts (Event Review Board). All events of clinical brain metastasis progression were included, regardless of whether the event occurred while the participant was still receiving study treatment or had previously discontinued study treatment. If a participant did not have an event of clinical brain metastases progression, their data were censored at the date of the last available clinical disease progression assessment. Time to clinical brain metastasis progression was estimated for each treatment group using Kaplan-Meier methodology.
    Time Frame
    From randomization up to 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    99 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subject must have cytologically or histologically confirmed non-small cell lung cancer Subject must have brain metastases demonstrated on a magnetic resonance imaging (MRI) brain scan. Subject must be eligible for treatment with WBRT Subject must have had adequate hematologic, renal, and hepatic function. Exclusion Criteria: Subject is diagnosed with brain metastases greater than 28 days prior to Day 1 Subject received any prior form of cranial radiation and/or neurosurgery for their brain metastases Subject's last dose of anti-cancer therapy or investigational therapy was less than or equal to 7 days prior to Day 1 Subject has a Karnofsky Performance Score of less than 70 Subject has significant dyspnea requiring supplemental oxygen therapy Subject has liver metastases (restaging is not required for known liver metastases) Subject has more than 2 sites (organ systems) of metastases from non-small cell lung cancer with the exception of intra-cranial sites of metastases from non-small cell lung cancer, thoracic sites of metastases from non-small cell lung cancer and bone metastases Subject has leptomeningeal metastases or subarachnoid spread of tumor Subject has unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment Subject has a known seizure disorder that is uncontrolled, or has seizures occurring greater than or equal to 3 times a week over the past month. Subjects presenting with symptoms of seizures from the brain metastases are eligible; however he/she should receive adequate anti-seizure medication prior to study treatment Subject is pregnant or lactating Subject has previously been treated with a poly-(ADP-ribose)-polymerase inhibitor as an investigational agent Subject has clinically significant and uncontrolled major medical condition(s) Subject has a history of another active cancer within the past 5 years except: cervical cancer in situ, in situ carcinoma of the bladder, basal or squamous cell carcinoma of the skin or other cancer in situ that is considered cured
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Vincent Giranda, MD
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    27655223
    Citation
    Chabot P, Hsia TC, Ryu JS, Gorbunova V, Belda-Iniesta C, Ball D, Kio E, Mehta M, Papp K, Qin Q, Qian J, Holen KD, Giranda V, Suh JH. Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study. J Neurooncol. 2017 Jan;131(1):105-115. doi: 10.1007/s11060-016-2275-x. Epub 2016 Sep 21.
    Results Reference
    result

    Learn more about this trial

    Comparison of Veliparib and Whole Brain Radiation Therapy (WBRT) Versus Placebo and WBRT in Adults With Brain Metastases From Non-Small Cell Lung Cancer

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