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

Neoplasm Metastasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00649207
• Other study ID #: M10-128
• Status: Completed
• Phase: Phase 1
• First received: March 28, 2008
• Last updated: November 17, 2017
• Start date: March 2008
• Est. completion date: March 2013

Study information

• Verified date: May 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Diseases
• Brain Neoplasms
• Central Nervous System Diseases
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Second Primary
• Nervous System Diseases
• Nervous System Neoplasms

Intervention

Drug:
• ABT-888
Oral Capsules

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

Locations

Country	Name	City	State
Canada	Site Reference ID/Investigator# 18542	Toronto
Puerto Rico	Site Reference ID/Investigator# 46322	Ponce
United States	Site Reference ID/Investigator# 8334	Atlanta	Georgia
United States	Site Reference ID/Investigator# 7180	Baltimore	Maryland
United States	Site Reference ID/Investigator# 52462	Chicago	Illinois
United States	Site Reference ID/Investigator# 19021	Detroit	Michigan
United States	Site Reference ID/Investigator# 24483	Kansas City	Kansas
United States	Site Reference ID/Investigator# 6653	Madison	Wisconsin
United States	Site Reference ID/Investigator# 6344	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

References & Publications (1)

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 metasta — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Safety Assessment Physical and Neurological Exam		be performed at all study visits, final and follow-up visit
Secondary	Safety Assessment Mini-Mental State Examination		be performed at all study visits, final and follow-up visit
Secondary	Safety Assessment Laboratory testing	Chemistry and Hematology labs will be collected	be performed at all study visits, final and follow-up visit