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Glioblastoma MultiformePhase 2NCT01124539

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

A Phase 2 study testing AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin) in people with Glioblastoma Multiforme and GBM, run by Arno Therapeutics at 9 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma Multiforme, GBM, Gliosarcoma
What is being tested?
AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
9 sitesin 2 countries
Study dates
Dec 2009to Feb 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • 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.
  • Demonstrated, in the opinion of the investigator, the ability to follow directions necessary to participate in the clinical trial.
  • 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.
  • A life expectancy of greater than 2 months.

Who cannot join

  • 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.
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  • 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):
  • 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
  • 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
  • Progressive disease with any topoisomerase I inhibitors.
  • History of anaphylactic injection reaction of > Grade 3 to any product used to formulate AR-67.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

United States7 sites

  • Northwestern University - Robert H Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • The Ohio State University - James Comprehensive Cancer Center

    Columbus, Ohio, 43210

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

    Durham, North Carolina, 27710

  • North Shore - Long Island Jewish Hospital/Monter Cancer Center

    Lake Success, New York, 11042

  • University of Kentucky - Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Utah - Huntsman Cancer Center

    Salt Lake City, Utah, 84112

  • Derrick L Davis Forsyth Regional Cancer Center

    Winston-Salem, North Carolina, 27103

Other trials in United States

Canada2 sites

  • University of Calgary - Tom Baker Cancer Center

    Calgary, Alberta, T2N 4N2

  • University of Alberta - Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

Other trials in Canada

About this study

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

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.

Being tested
AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin)
Keywords
Adult Patients, Recurrence of Glioblastoma Multiforme, Recurrence of GBM, Gliosarcoma
Medical subject headings
Glioblastoma, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called AR67, formerly DB-67, formerly DB67

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

Study groups in NCT01124539
Study groupRoleWhat they receive
AR-67ExperimentalNot described
Receives: Drug: AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

    Measured: 6 month PFS

  2. 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).

    Measured: 2 month PFS

Secondary outcomes (5)

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

    Measured: 1 year

  2. the effect of AR-67 on overall PFS

    Measured: 6 Months

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

    Measured: 6 Months

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

    Measured: 6 Months

  5. the safety and tolerability of AR-67

    Measured: 6 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2010 (estimated)
  2. Study startDec 2009
  3. Primary completionSep 2014
  4. Study completionFeb 2015 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01124539
Sponsor's protocol ID
ARN-AR67-IIS202
Status last verified
Jan 2014
First submitted
12 May 2010
Last updated
9 Dec 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AR-67 (7-t-butyldimethylsiltyl-10-hydroxy-camptothecin) in people with Glioblastoma Multiforme and GBM, run by Arno Therapeutics at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01124539.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2014.

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