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

NCT00649207 | Completed Phase 1

• 1 other identifier: M10-128
• Study Type: interventional
• Target: 80
• Locations: 3 countries
• Sites: 9

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.

Conditions

Brain Diseases; Brain Neoplasms; Central Nervous System Diseases; Neoplasm Metastasis; Nervous System Neoplasms

Keywords

WBRT; Brain Metastases; Radiation; ABT-888; PARP

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (1)

1

EXPERIMENTAL

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; Radiation: Whole Brain Radiation Therapy

Interventions

ABT-888 DRUG

Oral Capsules

Also known as: veliparib

1

Whole Brain Radiation Therapy RADIATION

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

Also known as: WBRT

1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Study Sites (9)

Site Reference ID/Investigator# 8334

Atlanta, Georgia, 30322, United States

Location

Site Reference ID/Investigator# 52462

Chicago, Illinois, 60611, United States

Location

Site Reference ID/Investigator# 24483

Kansas City, Kansas, 66160, United States

Location

Site Reference ID/Investigator# 7180

Baltimore, Maryland, 21231-2410, United States

Location

Site Reference ID/Investigator# 19021

Detroit, Michigan, 48202-2689, United States

Location

Site Reference ID/Investigator# 6344

Philadelphia, Pennsylvania, 19111, United States

Location

Site Reference ID/Investigator# 6653

Madison, Wisconsin, 53792, United States

Location

Site Reference ID/Investigator# 18542

Toronto, M5G 2M9, Canada

Location

Site Reference ID/Investigator# 46322

Ponce, 00716, Puerto Rico

Location

Related 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 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.

  PMID: 25682091 RESULT

MeSH Terms

Conditions

Brain Diseases; Brain Neoplasms; Central Nervous System Diseases; Neoplasm Metastasis; Nervous System Neoplasms

Interventions

veliparib

Condition Hierarchy (Ancestors)

Nervous System Diseases; Central Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shepherd L Stacie, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2008
• First Posted: April 1, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: November 21, 2017

Record last verified: 2013-05

Locations

US (7); PR (1); CA (1)