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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

Phase 1
18 Years
Not Enrolling
Brain Diseases, Brain Neoplasms, Central Nervous System Diseases, Neoplasm Metastasis, Nervous System Neoplasms

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Trial Information

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 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.

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

- 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

- 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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the maximum tolerated dose of ABT-888 in combination with whole brain radiation therapy

Outcome 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.

Safety Issue:


Principal Investigator

Shepherd L Stacie, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

March 2008

Completion Date:

March 2013

Related Keywords:

  • Brain Diseases
  • Brain Neoplasms
  • Central Nervous System Diseases
  • Neoplasm Metastasis
  • Nervous System Neoplasms
  • WBRT
  • Brain Metastases
  • Radiation
  • ABT-888
  • PARP
  • Brain Diseases
  • Brain Neoplasms
  • Neoplasms
  • Central Nervous System Diseases
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Nervous System Diseases
  • Nervous System Neoplasms



Site Reference ID/Investigator# 8334Atlanta, Georgia  30322
Site Reference ID/Investigator# 52462Chicago, Illinois  60611
Site Reference ID/Investigator# 24483Kansas City, Kansas  66160
Site Reference ID/Investigator# 7180Baltimore, Maryland  21231-2410
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Site Reference ID/Investigator# 6653Madison, Wisconsin  53792