Study of AR-67 in Adult Patients With Recurrence of Glioblastoma Multiforme (GBM) or Gliosarcoma

NCT01124539 | Unknown Phase 2

• 1 other identifier: ARN-AR67-IIS202
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 9

Brief Summary

The primary objective of this study is to determine the 6-month Progression free survival (PFS) when intravenous (IV) AR-67 is administered in adults with confirmed recurrence of GBM who have not recently (\> 90 days) recurred after treatment bevacizumab (including patients who've received temazolamide, but no bevacizumab). The primary objective in the rapid bevacizumab failure group (\< 90 days) is to determine the 2-month PFS.

Conditions

Glioblastoma Multiforme; GBM; Gliosarcoma

Keywords

Adult Patients; Recurrence of Glioblastoma Multiforme; Recurrence of GBM; Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Determine the 6-month Progression free survival (PFS) AR-67 is administered in adults with confirmed recurrence of GBM who have not recently (> 90 days) recurred after treatment bevacizumab.

  Thirty-two (32) patients will be accrued to the non-bevacizumab failure cohort.

  6 month PFS

• The primary objective in the rapid bevacizumab failure group (< 90 days) is to determine the 2-month PFS.

  26 subjects will be enrolled in the second cohort (Rapid Avastin Progressors).

  2 month PFS

Secondary Outcomes (5)

• the effect of AR-67 on overall survival (OS)

  1 year

• the effect of AR-67 on overall PFS

  6 Months

• the effect of AR-67 on event-free survival (EFS)

  6 Months

• the impact of AR-67 on tumor response in patients with measurable disease

  6 Months

• the safety and tolerability of AR-67

  6 Months

Study Arms (1)

AR-67

EXPERIMENTAL

Drug: AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin)

Interventions

AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin) DRUG

IV AR-67 administered once daily for 5 days on an every 21-day cycle

Also known as: AR67, formerly DB-67, formerly DB67

AR-67

Eligibility Criteria

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

You may qualify if:

• Male or female age 18 years or older.
• Patient, or legal representative, able to provide study-specific informed consent after risks and benefits of treatment have been explained prior to screening.
• Confined histopathology of World Health Organization (WHO) Grade IV GBM or Gliosarcoma at primary diagnosis or recurrence by local pathology review.
• Unequivocal radiographic evidence of recurrence of tumor by MRI within 14 days prior to enrollment.
• Patients who have progressed, had surgery, and have no measurable disease are eligible as long as they have adequately recovered from the surgery.
• Received prior radiotherapy and temozolomide treatment.
• Received last chemotherapy or biologic therapy treatment ≥14 days before first dose of study drug (≥42 days if nitrosourea or ≥90 days if bevacizumab for the non-bevacizumab failure cohort or therapeutic antibody was administered) or, for daily type regimens, ≥7 days or 5 half-lives of the drugs' pharmacokinetics/dynamics or biologic activities, whichever is longer, before the first dose of study drug. For subjects that have received prior chemotherapy, all toxicities need to have resolved ≤ Grade 1 prior to the administration of study drug. For the patients in the bevacizumab failure cohort, failure must have occurred within the prior 90 days of receiving the last bevacizumab dose.
• Completed radiotherapy ≥90 days before study starts.
• Completed the administration of any investigational agent ≥14 days or 5 half-lives of the drugs' PK/dynamics or biologic activities, whichever is longer, before study starts.
• Karnofsky performance status of ≥60%.
• Recovered to Grade 1 or less from the toxic effects of any earlier intervention.
• Patients receiving EIADs must be switched to non-EIADs at least 14 days prior to study start.
• Adequate renal, liver, and bone marrow function according to the following criteria:
• Absolute neutrophil count ≥1500/mcL
• Platelets ≥150,000/mcL

You may not qualify if:

• Patients on therapeutic Coumadin; however, patients on therapeutic Coumadin that can switch to low molecular weight heparin (LMWH) at least 7 days prior to first dosing will be eligible for study participation.
• Female patients who are pregnant or breastfeeding.
• Prior malignancy other than curatively treated basal cell or cervical carcinoma in situ or adequately treated Stage I or II cancer from which the patient is currently in complete remission and from which the patient has been disease-free for three years.
• Uncontrolled concurrent illness including active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known HIV infection.
• Any other condition that would compromise treatment and/or evaluation with reasonable safety.
• Completed intracranial surgery ≤ 14 days before the study starts.
• Received an anti-epilpetic drug, which is a CYP3A4 inducer from ≤ 14 days prior to screening until study end. See Appendix 1 for the list of enzyme inducing anti-epileptic drugs.
• Inducers of CYP3A4 may also alter the metabolism of AR-67. The following list of CYP3A4 inducers are prohibited from 14 days prior to screening through discontinuation from the study:
• HIV: efavirenz, nevirapine
• Antibiotics: rifampin (rifampicin), rifabutin, rifapentine
• Antiretrovirals: efavirenz, nevirapine
• Miscellaneous: St. John's Wort, modafinil
• Anti-Epileptic Drugs: phenytoin, phenobarbital, primidone, carbamazapine, oxcarbazapine and topiramate
• Co-administration of AR-67 and medications that are substrates for the CYP450 enzymes and have the potential to cause serious and/or life-threatening AE's is prohibited. These medications include (but are not limited to):

Sponsors & Collaborators

• Arno Therapeutics: lead

Study Sites (9)

Northwestern University - Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

North Shore - Long Island Jewish Hospital/Monter Cancer Center

Lake Success, New York, 11042, United States

Location

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

Durham, North Carolina, 27710, United States

Location

Derrick L Davis Forsyth Regional Cancer Center

Winston-Salem, North Carolina, 27103, United States

Location

The Ohio State University - James Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Utah - Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

University of Calgary - Tom Baker Cancer Center

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta - Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

7-tert-butyldimethylsilyl-10-hydroxycamptothecin

Condition Hierarchy (Ancestors)

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

Study Officials

• James J Vredneburgh, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2010
• First Posted: May 17, 2010
• Study Start: December 1, 2009
• Primary Completion: September 1, 2014
• Study Completion: February 1, 2015
• Last Updated: December 9, 2014

Record last verified: 2014-01

Locations

US (7); CA (2)