GliomaPhase 1NCT00979173
Pharmacokinetics (PK) Study of AC480 for Recurrent Glioma
A Phase 1 study testing AC480 in people with Glioma, run by Annick Desjardins at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- AC480
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Jun 2012
- Phase
- Phase 1
- 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
- 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%
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- 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.
- An interval of a least 4 weeks from exposure to investigational agents, unless there is unequivocal evidence of tumor progression and the patients has recovered from all anticipated toxicities from prior therapy.
- Signed written informed consent including HIPAA language according to institutional guidelines. This informed consent shall include language whereby Ambit shall have access to the patient's protected health information. A signed informed consent must be obtained prior to any study specific procedures.
- If sexually active, patients will take contraceptive measures for the duration of the treatments and for 3 months following discontinuation of AC480.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (sensitivity < or = to 25IU HCG/L) within 72 hours prior to the start of study drug administration. Males and females age ≥ 18 years. WOCBP include any female that has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not post menopausal (defined as amenorrhea > 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/mL). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or are practicing abstinence or where the partner is sterile (e.g., vasectomy), should be considered to be of childbearing potential.
- Patients having received bevacizumab are eligible four weeks after the last dose of bevacizumab.
Who cannot join
- 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.
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- 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);
- Any history of second or third degree heart block;
- Heart rate < 50 / minute on pre-entry electrocardiogram;
- Uncontrolled hypertension.
- Human immunodeficiency virus (HIV) positivity.
- Active hepatitis (hep) B or C or other active liver disease.
- Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3) (see Inclusion Criteria).
- Drugs (or medical conditions) that are generally accepted to have a risk of causing torsades de pointes (see Appendix E). Subjects who have discontinued any of these medications must have a wash-out period of at least 5 days or 5 half-lives of the drug (whichever is greater) prior to the first dose of AC480.
- Proton pump inhibitors and histamine H2 antagonists. Other antacid agents may be taken, but not within 8 hours before or 4 hours after dosing of AC480. A detailed log recording administration of other antacids in relation to AC480 must be kept.
- Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize subject safety or interfere with the objectives of the study.
- Patient is < 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ.
- Concurrent administration of warfarin, rifampin or St. John's Wort, except for low-dose warfarin (1mg po DAILY).
- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Pharmacokinetic Study of AC480 Administered Twice Daily in Surgically Resectable Malignant Glioma Patients Not on Enzyme-Inducing Anticonvulsants
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).
Read the detailed description
Plasma and tumoral pharmacokinetics, as well as FDG-PET data will be analyzed to determine the intratumoral and plasma levels of AC480 obtained and its antiproliferative activity. After recovery from surgery, all patients will resume AC480 at 300 mg orally BID until evidence of disease progression or toxicity (Part II: Maintenance Therapy). Those patients will be followed for determination of 6-month progression free survival. Patients will remain on treatment for as long as they have clinical benefit from the treatment. There will be no limit to the number of cycles of treatment a patient can receive providing they continue to benefit from and are not intolerant to AC480 administration.
The data collected in this study will be summarized in tables listing the mean, standard deviation, and number of patients for continuous data, or in tables listing count and percentage for categorical data, where appropriate. All patient data will be listed by patient or by parameter, all statistical analyses will be performed and all data appendices will be created by using the SAS system. Pharmacokinetic analysis will be made to determine if AC480 reaches the intracerebral tumor tissue. Comparisons will be made between the data obtained from the plasma of the same patients treated on AC480, including determination of the tumor-to-plasma ratio. The most common side effects of AC480 are generally mild to moderate in severity and include: nausea, vomiting, diarrhea, fatigue, cough, elevation of the liver enzymes, anemia, and rash.
- Conditions
- Glioma
- Being tested
- AC480
- Keywords
- malignant glioma, glioblastoma multiforme, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, Pro00018751, Duke, Ambit, AC480
- Medical subject headings
- Glioma, Glioblastoma, Gliosarcoma, Astrocytoma, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AC480Drug
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: AC480 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intratumoral and plasma pharmacokinetics of AC480 will be obtained on surgical tissue specimens from 5 patients treated pre-operatively with AC480.
Measured: At time of resection
Secondary outcomes (5)
Anti-proliferative effect of AC480 by FDG-PET
Measured: 2 weeks
Intratumoral and plasma pharmacodynamics of AC480
Measured: 6 months
6-month progression-free survival (PFS)
Measured: 6 months
Radiographic response
Measured: 6 months
Adverse event and toxicity monitoring
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2009 (estimated)
- Study startNov 2009
- Primary completionOct 2010
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Annick Desjardins
- Sponsor type
- University, hospital or other
- Collaborators
- Ambit Biosciences Corporation
- Responsible party
- Sponsor-investigator, Annick Desjardins, Duke University
- Investigators
- Annick Desjardins, MD, FRCPC, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00979173
- Sponsor's protocol ID
- Pro00018751
- Status last verified
- Dec 2013
- First submitted
- 6 Aug 2009
- Last updated
- 29 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacokinetic Study of AC480 Administered Twice Daily in Surgically Resectable Malignant Glioma Patients Not on Enzyme-Inducing Anticonvulsants
- ClinicalTrials.gov ID
- NCT00979173
- Acronym / sponsor ID
- Pro00018751
- Conditions
- Glioma
- Keywords
- malignant glioma, glioblastoma multiforme, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma, Pro00018751, Duke
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Annick DesjardinsUniversity, hospital or other
- Collaborators
- Ambit Biosciences Corporation
- Study start
- Nov 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 17 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Plasma and tumoral pharmacokinetics, as well as FDG-PET data will be analyzed to determine the intratumoral and plasma levels of AC480 obtained and its antiproliferative activity. After recovery from surgery, all patients will resume AC480 at 300 mg orally BID until evidence of disease progression or toxicity (Part II: Maintenance Therapy). Those patients will be followed for determination of 6-month progression free survival. Patients will remain on treatment for as long as they have clinical benefit from the treatment. There will be no limit to the number of cycles of treatment a patient can receive providing they continue to benefit from and are not intolerant to AC480 administration.
The data collected in this study will be summarized in tables listing the mean, standard deviation, and number of patients for continuous data, or in tables listing count and percentage for categorical data, where appropriate. All patient data will be listed by patient or by parameter, all statistical analyses will be performed and all data appendices will be created by using the SAS system. Pharmacokinetic analysis will be made to determine if AC480 reaches the intracerebral tumor tissue. Comparisons will be made between the data obtained from the plasma of the same patients treated on AC480, including determination of the tumor-to-plasma ratio. The most common side effects of AC480 are generally mild to moderate in severity and include: nausea, vomiting, diarrhea, fatigue, cough, elevation of the liver enzymes, anemia, and rash.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AC480 | Experimental | Drug: AC480Patients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AC480Subjects 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). | Drug | AC480 |
Primary outcome
Intratumoral and plasma pharmacokinetics of AC480 will be obtained on surgical tissue specimens from 5 patients treated pre-operatively with AC480.
Time frame: At time of resection
5 secondary outcomes
Anti-proliferative effect of AC480 by FDG-PET
Time frame: 2 weeks
Intratumoral and plasma pharmacodynamics of AC480
Time frame: 6 months
6-month progression-free survival (PFS)
Time frame: 6 months
Radiographic response
Time frame: 6 months
Adverse event and toxicity monitoring
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2014.
- The Preston Robert Tisch Brain Tumor CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annick Desjardins, MD, FRCPC principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AC480 in people with Glioma, run by Annick Desjardins at 1 site in United States.
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 20 inclusion and 27 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: finished, as of the sponsor's last update on 29 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Intratumoral and plasma pharmacokinetics of AC480 will be obtained on surgical tissue specimens from 5 patients treated pre-operatively with AC480. (time frame: At time of resection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Jan 2014.