Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma

NCT00979173 | Completed Phase 1

• 1 other identifier: Pro00018751
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective is to evaluate the intratumoral and plasma pharmacokinetics of AC480 among patients who are candidates for a resection with a recurrent malignant glioma who are not on CYP-3A enzyme inducing anti-epileptic drugs (EIAEDS). Secondary objectives include the following: to evaluate the antiproliferative effect of AC480 by FDG-PET Scan; to evaluate the safety and tolerability of AC480; and, to describe 6-month progression-free survival (PFS) and radiographic response. This is a single institution, open label, pharmacokinetic study of AC480 in patients with recurrent malignant glioma. The study will enroll 5 patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection for preoperative treatment with AC480 at 300 mg orally twice daily (BID) for 14 (plus or minus 2) days before surgery (Part I- Induction Therapy). After surgery (Part II- Maintenance Therapy), patients will continue to be dosed with AC480 until disease progression or intolerance, and will be evaluated after every other cycle (1 cycle is 28 days).

Conditions

Glioma

Keywords

malignant glioma; glioblastoma multiforme; gliosarcoma; anaplastic astrocytoma; anaplastic oligodendroglioma; anaplastic mixed glioma; Pro00018751; Duke; Ambit; AC480

Outcome Measures

Primary Outcomes (1)

• Intratumoral and plasma pharmacokinetics of AC480 will be obtained on surgical tissue specimens from 5 patients treated pre-operatively with AC480.

  At time of resection

Secondary Outcomes (5)

• Anti-proliferative effect of AC480 by FDG-PET

  2 weeks

• Intratumoral and plasma pharmacodynamics of AC480

  6 months

• 6-month progression-free survival (PFS)

  6 months

• Radiographic response

  6 months

• Adverse event and toxicity monitoring

  6 months

Study Arms (1)

AC480

EXPERIMENTAL

Patients who are not on enzyme inducing anti-epileptic drugs (EIAEDs) and are scheduled to undergo salvage surgical resection treated with preoperative AC480 at 300 mg BID followed by post-surgical AC480 at 300 mg BID.

Drug: AC480

Interventions

AC480 DRUG

Subjects will be initiated on AC480 300mg orally BID for 14 (+/-2 days) before surgery. After surgery, subjects will continue to be dosed with AC480 until either disease progression or intolerance, and will be evaluated every other cycle (i.e., every 4 weeks).

AC480

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed diagnosis of a recurrent/progressive WHO grade 4 malignant glioma (glioblastoma multiforme or gliosarcoma) or WHO grade 3 malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic mixed glioma) and be surgical candidates. Recurrence will be defined based on the modified MacDonald criteria or based on histopathologic confirmation of tissue obtained via surgical intervention. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO grade III or IV malignant glioma.
• Greater than or equal to 18 years old.
• Karnofsky Performance Status (KPS) greater than or equal to 60%.
• Patients must be presenting in first, second or third relapse. Relapse is defined as progression following anti-cancer therapy other than surgery, including non-surgical therapies that are considered standard treatment for high-grade glioma if administered to patients with prior low-grade glioma. Prior therapy must have included external beam radiotherapy.
• Adequate bone marrow, liver and renal function as assessed by the following:
• Hematocrit \> or = to 29%
• Absolute neutrophil count (ANC) \> or = to 1,500/mL
• Platelet count \> or = to 125,000/mL
• Total bilirubin \< or = to 1.5 x ULN
• ALT and AST \< or equal to 2.5 x the ULN
• INR \< 1.5 or a PT/PTT within normal limits (unless on therapeutic anti-coagulation). Patients receiving anti-coagulation treatment with a low-molecular weight heparin will be allowed to participate, however oral warfarin is not permitted except for low-dose warfarin (1mg po DAILY).
• Creatinine \< or = to 1.5 x ULN
• Serum Na, K+, Mg2+, Phosphate and Ca2+ Within Normal Limit (WNL)
• An interval of at least 12 weeks from completion of standard, daily XRT, unless one of the following occurs: a) new area of enhancement on MRI imaging that is outside the XRT field; b) biopsy proven recurrent tumor; c) radiographic evidence of progressive tumor on 2 consecutive scans at least 4 weeks apart.
• An interval of at least 4 weeks from prior chemotherapy (except nitrosoureas which require 6 weeks) unless there is unequivocal evidence of tumor progression and the patient has recovered from all anticipated toxicities from prior therapy.

You may not qualify if:

• Subjects on enzyme-inducing antiepileptic drugs (phenytoin, phenobarbitol, carbamazepine, oxcarbamazepine, and primidone).
• Subjects previously treated with targeted therapies to EGFR and HER2.
• More than 3 prior episodes of progressive disease.
• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 3 months after completion of the study.
• Women who are pregnant or breastfeeding.
• Men who are unwilling or unable to use an acceptable method of birth control if their sexual partners are WOCBP for the entire study period and for at least 3 months after completion of the study.
• A serious uncontrolled medical disorder or active infection requiring IV antibiotics, which would impair the ability of the subject to receive protocol therapy.
• Uncontrolled or significant cardiovascular disease, including:
• A myocardial infarction within 12 months;
• Uncontrolled angina within 6 months;
• Congestive heart failure NYHA class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram (ECHO) performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%;
• Diagnosed or suspected long QT syndrome;
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes);
• Any subject with a history of any arrhythmia should be discussed with the Ambit Medical Monitor prior to entry into the study;
• Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec);

Sponsors & Collaborators

• Annick Desjardins: lead
• Ambit Biosciences Corporation: collaborator

Study Sites (1)

The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center

MeSH Terms

Conditions

Glioma; Glioblastoma; Gliosarcoma; Astrocytoma; Oligodendroglioma

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Annick Desjardins, MD, FRCPC

  Duke Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assist Professor of Medicine-Neurology

Study Record Dates

• First Submitted: August 6, 2009
• First Posted: September 17, 2009
• Study Start: November 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: June 1, 2012
• Last Updated: January 29, 2014

Record last verified: 2013-12

Locations

US (1)