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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01124539
Recruitment Status : Unknown
Verified January 2014 by Arno Therapeutics.
Recruitment status was:  Active, not recruiting
First Posted : May 17, 2010
Last Update Posted : December 9, 2014
Information provided by (Responsible Party):
Arno Therapeutics

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme GBM Gliosarcoma Drug: AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin) Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin) in Adult Patients With Recurrence of Glioblastoma Multiforme (GBM) or Gliosarcoma
Study Start Date : December 2009
Actual Primary Completion Date : September 2014
Estimated Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: AR-67 Drug: AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin)
IV AR-67 administered once daily for 5 days on an every 21-day cycle
Other Names:
  • AR67
  • formerly DB-67
  • formerly DB67

Primary Outcome Measures :
  1. 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. [ Time Frame: 6 month PFS ]
    Thirty-two (32) patients will be accrued to the non-bevacizumab failure cohort.

  2. The primary objective in the rapid bevacizumab failure group (< 90 days) is to determine the 2-month PFS. [ Time Frame: 2 month PFS ]
    26 subjects will be enrolled in the second cohort (Rapid Avastin Progressors).

Secondary Outcome Measures :
  1. the effect of AR-67 on overall survival (OS) [ Time Frame: 1 year ]
  2. the effect of AR-67 on overall PFS [ Time Frame: 6 Months ]
  3. the effect of AR-67 on event-free survival (EFS) [ Time Frame: 6 Months ]
  4. the impact of AR-67 on tumor response in patients with measurable disease [ Time Frame: 6 Months ]
  5. the safety and tolerability of AR-67 [ Time Frame: 6 Months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female age 18 years or older.
  2. Patient, or legal representative, able to provide study-specific informed consent after risks and benefits of treatment have been explained prior to screening.
  3. Confined histopathology of World Health Organization (WHO) Grade IV GBM or Gliosarcoma at primary diagnosis or recurrence by local pathology review.
  4. Unequivocal radiographic evidence of recurrence of tumor by MRI within 14 days prior to enrollment.
  5. Patients who have progressed, had surgery, and have no measurable disease are eligible as long as they have adequately recovered from the surgery.
  6. Received prior radiotherapy and temozolomide treatment.
  7. 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.
  8. Completed radiotherapy ≥90 days before study starts.
  9. 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.
  10. Karnofsky performance status of ≥60%.
  11. Recovered to Grade 1 or less from the toxic effects of any earlier intervention.
  12. Patients receiving EIADs must be switched to non-EIADs at least 14 days prior to study start.
  13. Adequate renal, liver, and bone marrow function according to the following criteria:

    • Absolute neutrophil count ≥1500/mcL
    • Platelets ≥150,000/mcL
    • Total bilirubin within upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 2.5 X institutional ULN
    • Creatinine within normal limits or creatinine clearance ≥ 50 mL/min for patients with creatinine levels above normal limits.
  14. Demonstrated, in the opinion of the investigator, the ability to follow directions necessary to participate in the clinical trial.
  15. Women of childbearing potential must agree to use acceptable contraceptive methods as follows:

    • An intrauterine device with a documented failure rate of less than 1% per year.
    • Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female.
    • Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product.
    • Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide, or male condom and diaphragm with spermicide).

    Note: These methods are to be used consistently and in accordance with both the product label and the instructions of the treating physician. Oral contraceptives are not reliable due to potential drug-drug interactions and should be used with caution if the patient insists on their use as a contraceptive.

  16. A life expectancy of greater than 2 months.

Exclusion Criteria:

  1. 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.
  2. Female patients who are pregnant or breastfeeding.
  3. 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.
  4. 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.
  5. Known HIV infection.
  6. Any other condition that would compromise treatment and/or evaluation with reasonable safety.
  7. Completed intracranial surgery ≤ 14 days before the study starts.
  8. 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
  9. 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):

    • Anticoagulants: therapeutic coumadin
    • Oral hypoglycemics: glilpizide, glyburide, tolbutamide, glimepiride, nateglinice
    • Erectile dysfunction agents: sildenafil, tadalafil, vardenafil
    • Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, methylergonovine
    • Neuroleptics: pimozide
    • Antiarrhythmics: bepridil, flecainide, lidocaine, meziletine, amiodarone, quinidine, propafenone
    • Immune modulators: cyclosporine, tacrolimus, sirolimus
    • Miscellaneous: theophylline, quetiapine, risperidone, tacrine, clozapine, atomoxetine
  10. The following list of CYP3A4 inhibitors are prohibited from 14 days prior to screening through discontinuation from the study:

    • Antibiotics: clarithromycin, erythromycin, troleandomycin
    • HIV: antiretrovirals (delaviridine), protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir)
    • Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole (>150 mg daily)
    • Antidepressants: nefazodone, fluvoxamine
    • Calcium channel blockers: verapamil, diltiazem
    • Gastrointestinal: cimetidine, aprepitant
    • Miscellaneous: grapefruit or its juice
  11. Progressive disease with any topoisomerase I inhibitors.
  12. History of anaphylactic injection reaction of > Grade 3 to any product used to formulate AR-67.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01124539

United States, Illinois
Northwestern University - Robert H Lurie Comprehensive Cancer Center
Chicago, Illinois, United States, 60611
United States, Kentucky
University of Kentucky - Markey Cancer Center
Lexington, Kentucky, United States, 40536
United States, New York
North Shore - Long Island Jewish Hospital/Monter Cancer Center
Lake Success, New York, United States, 11042
United States, North Carolina
Duke University Medical Center - The Preston Robert Tisch Brain Tumor Center
Durham, North Carolina, United States, 27710
Derrick L Davis Forsyth Regional Cancer Center
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
The Ohio State University - James Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
United States, Utah
University of Utah - Huntsman Cancer Center
Salt Lake City, Utah, United States, 84112
Canada, Alberta
University of Calgary - Tom Baker Cancer Center
Calgary, Alberta, Canada, T2N 4N2
University of Alberta - Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Sponsors and Collaborators
Arno Therapeutics
Principal Investigator: James J Vredneburgh, MD Duke University Medical Center - The Preston Robert Tisch Brain Tumor Center

Responsible Party: Arno Therapeutics Identifier: NCT01124539     History of Changes
Other Study ID Numbers: ARN-AR67-IIS202
First Posted: May 17, 2010    Key Record Dates
Last Update Posted: December 9, 2014
Last Verified: January 2014

Keywords provided by Arno Therapeutics:
Adult Patients
Recurrence of Glioblastoma Multiforme
Recurrence of GBM

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Disease Attributes
Pathologic Processes
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action