Clinical trial NCT00649207: A Phase I Study of ABT-888 in Combination With Conventional Whole Brain Radiation Therapy (WBRT) in Cancer Patients With Brain Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain Diseases
Brain Neoplasms
Central Nervous System Diseases
Neoplasm Metastasis
Nervous System Neoplasms
Keywords: WBRT
Brain Metastases
Radiation
ABT-888
PARP
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2008-04-01
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine the maximum tolerated dose of ABT-888 in combination with whole brain radiation therapy
timeFrame: 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.
Secondary outcomes:
measure: Safety Assessment Physical and Neurological Exam
timeFrame: be performed at all study visits, final and follow-up visit
measure: Safety Assessment Mini-Mental State Examination
timeFrame: be performed at all study visits, final and follow-up visit
measure: Safety Assessment Laboratory testing
timeFrame: be performed at all study visits, final and follow-up visit
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Site Reference ID/Investigator# 8334
state: Georgia
city: Chicago
country: United States
facility: Site Reference ID/Investigator# 52462
state: Illinois
city: Kansas City
country: United States
facility: Site Reference ID/Investigator# 24483
state: Kansas
city: Baltimore
country: United States
facility: Site Reference ID/Investigator# 7180
state: Maryland
city: Detroit
country: United States
facility: Site Reference ID/Investigator# 19021
state: Michigan
city: Philadelphia
country: United States
facility: Site Reference ID/Investigator# 6344
state: Pennsylvania
city: Madison
country: United States
facility: Site Reference ID/Investigator# 6653
state: Wisconsin
city: Toronto
country: Canada
facility: Site Reference ID/Investigator# 18542
city: Ponce
country: Puerto Rico
facility: Site Reference ID/Investigator# 46322
Study officials:
affiliation: AbbVie
name: Shepherd L Stacie, MD
role: STUDY_DIRECTOR
References:
citation: Mehta MP, Wang D, Wang F, Kleinberg L, Brade A, Robins HI, Turaka A, Leahy T, Medina D, Xiong H, Mostafa NM, Dunbar M, Zhu M, Qian J, Holen K, Giranda V, Curran WJ. Veliparib in combination with whole brain radiation therapy in patients with brain metastases: results of a phase 1 study. J Neurooncol. 2015 Apr;122(2):409-17. doi: 10.1007/s11060-015-1733-1. Epub 2015 Feb 15.