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

Sponsor

AbbVie (prior sponsor, Abbott) (Industry)

Overall Status

Completed

CT.gov ID

NCT00649207

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

8.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Diseases Brain Neoplasms Central Nervous System Diseases Neoplasm Metastasis Nervous System Neoplasms	Drug: ABT-888 Radiation: Whole Brain Radiation Therapy	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2008

Actual Primary Completion Date :

Mar 1, 2013

Actual Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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).	Drug: ABT-888 Oral Capsules Other Names: 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 Names: WBRT

Arm

Intervention/Treatment

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).

Drug: ABT-888

Oral Capsules

Other Names:

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 Names:

WBRT

Outcome Measures

Primary Outcome Measures

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

Safety Assessment Physical and Neurological Exam [be performed at all study visits, final and follow-up visit]
Safety Assessment Mini-Mental State Examination [be performed at all study visits, final and follow-up visit]
Safety Assessment Laboratory testing [be performed at all study visits, final and follow-up visit]
Chemistry and Hematology labs will be collected

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 8334	Atlanta	Georgia	United States	30322
2	Site Reference ID/Investigator# 52462	Chicago	Illinois	United States	60611
3	Site Reference ID/Investigator# 24483	Kansas City	Kansas	United States	66160
4	Site Reference ID/Investigator# 7180	Baltimore	Maryland	United States	21231-2410
5	Site Reference ID/Investigator# 19021	Detroit	Michigan	United States	48202-2689
6	Site Reference ID/Investigator# 6344	Philadelphia	Pennsylvania	United States	19111
7	Site Reference ID/Investigator# 6653	Madison	Wisconsin	United States	53792
8	Site Reference ID/Investigator# 18542	Toronto		Canada	M5G 2M9
9	Site Reference ID/Investigator# 46322	Ponce		Puerto Rico	00716