A Phase I Study of ABT-888 in Combination With Conventional Whole Brain Radiation Therapy (WBRT) in Cancer Patients With Brain Metastases

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT00649207
First received: March 28, 2008
Last updated: May 10, 2013
Last verified: May 2013

March 28, 2008
May 10, 2013
March 2008
March 2013   (final data collection date for primary outcome measure)
Determine the maximum tolerated dose of ABT-888 in combination with whole brain radiation therapy [ Time Frame: ABT-888 will be dose escalated until the largest dose is reached that is felt to be safe based on safety information from all subjects. ] [ Designated as safety issue: Yes ]
Maximum Tolerated Dose [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00649207 on ClinicalTrials.gov Archive Site
  • Safety Assessment Physical and Neurological Exam [ Time Frame: be performed at all study visits, final and follow-up visit ] [ Designated as safety issue: Yes ]
  • Safety Assessment Mini-Mental State Examination [ Time Frame: be performed at all study visits, final and follow-up visit ] [ Designated as safety issue: Yes ]
  • Safety Assessment Laboratory testing [ Time Frame: be performed at all study visits, final and follow-up visit ] [ Designated as safety issue: Yes ]
    Chemistry and Hematology labs will be collected
Not Provided
Not Provided
Not Provided
 
A Phase I Study of ABT-888 in Combination With Conventional Whole Brain Radiation Therapy (WBRT) in Cancer Patients With Brain Metastases
A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of ABT-888 in Combination With Whole Brain Radiation Therapy in Subjects With Brain Metastases

This Phase I clinical trial is studying the side effects and best dose of ABT-888 when given together with Whole Brain Radiation Therapy (WBRT) in treating patients with brain metastases.

This is a Phase 1, multicenter, dose-escalation study evaluating the safety, tolerability and pharmacokinetics of the PARP inhibitor ABT-888 in combination with conventional whole brain radiation therapy (WBRT) in the treatment of subjects with solid tumors metastatic to the brain.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain Diseases
  • Brain Neoplasms
  • Central Nervous System Diseases
  • Neoplasm Metastasis
  • Nervous System Neoplasms
  • Drug: ABT-888
    Oral Capsules
    Other Name: veliparib
  • Radiation: Whole Brain Radiation Therapy
    15 fractions of 2.5 Gy over 3 weeks to a total dose of 37.5 GY or 10 fractions of 3.0 Gy over 2 weeks to a total dose of 30 Gy
    Other Name: WBRT
Experimental: 1

This is an open label study; therefore, there are no numbered/labeled study arms.

This is a dose escalation study, ABT-888 dose will be escalated in conjunction with two schedules of whole brain radiation therapy (WBRT). Subjects may be treated WBRT for 3 weeks (15 days) or 2 weeks (10 days).

Interventions:
  • Drug: ABT-888
  • Radiation: Whole Brain Radiation Therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
80
March 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age is greater than or equal to 18 years.
  • Histologically or cytologically confirmed non-CNS primary solid malignancy.
  • Pathologically or radiographically confirmed metastatic disease in the brain. Subjects with non-measurable lesions, including leptomeningeal carcinomatosis, are eligible.
  • WBRT is clinically indicated, with the exception of prophylactic treatment.
  • Karnofsky Performance Status (KPS) greater than or equal to a score of 70.
  • Adequate hematology, renal and hepatic function.
  • Both men and women of childbearing potential must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and up to 2 months following completion of protocol therapy.

    • Total abstinence from sexual intercourse (minimum one complete menstrual cycle)
    • A vasectomized partner * Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration
    • Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream)
  • Subject is capable of understanding and complying with parameters as outlined in the protocol.
  • Subject or the subject's legally acceptable representative has voluntarily signed and dated the informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion Criteria:

  • Brain metastases secondary to germ cell tumor or lymphoma malignancy.
  • Primary central nervous system (CNS) neoplasm.
  • Prior or concurrent administration of the following therapies or treatments:

    • Prior treatment with WBRT
    • SRS performed less than 14 days prior to WBRT D1, or is scheduled to occur within 30 days of the last WBRT session
    • Last dose of chemotherapy, immunotherapy, biologic therapy, or investigational therapy was less than 14 days prior to WBRT D1. Bisphosphonates, hormone modification therapy, and trastuzumab are permitted without restriction
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or prior anti-cancer treatment.
  • Known seizure disorder (status epileptics) that is uncontrolled, or seizures occurring greater than or equal to 3 times a week over the past month.
  • If female, subject is pregnant or breast-feeding.
  • Clinically significant and uncontrolled major cardiac, respiratory, renal, hepatic, gastrointestinal, hematologic or neurological/psychiatric disease or disorder, including but not limited to:

    • Active uncontrolled infection
    • Symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
    • Any other illness condition(s) that could exacerbate potential toxicities, confound safety assessments, require excluded therapy for management, or limit compliance with study requirements
  • Unable to swallow and retain oral medications.
  • Known contraindication to enhanced MRI and CT, including but not limited to:

    • Presence of metal objects within the body such as a cardiac pacemaker, implanted cardiac defibrillator, brain aneurysm clips, cochlear implant, ocular foreign body, or shrapnel
    • History of immediate or delayed hypersensitivity reaction or other contraindication to contrast agents including but not limited to gadolinium and iodine
  • Previous enrollment in this study or another study involving the investigation of ABT-888, with the exception of receiving a single dose of study drug.
  • Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-888 and/or WBRT.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Puerto Rico
 
NCT00649207
M10-128
No
AbbVie ( AbbVie (prior sponsor, Abbott) )
AbbVie (prior sponsor, Abbott)
Not Provided
Study Director: Shepherd L Stacie, MD AbbVie
AbbVie
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP