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Adult Anaplastic AstrocytomaPhase 2NCT00499473

Sunitinib in Treating Patients With Recurrent Malignant Gliomas

A Phase 2 study testing sunitinib malate and pharmacological study in people with Adult Anaplastic Astrocytoma and Adult Diffuse Astrocytoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial is studying how well sunitinib works in treating patients with recurrent malignant gliomas. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
sunitinib malate and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
Jun 2007to Oct 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Stratum 1:
  • Currently not receiving an enzyme-inducing anticonvulsant
  • Patients receiving non-enzyme inducing anticonvulsants are eligible for this stratum
  • Histologically confirmed WHO grade IV astrocytoma (glioblastoma multiforme [GBM]) including gliosarcoma
  • Stratum 2 (USA patients only):
  • Currently on stable dose of an enzyme-inducing anticonvulsant (with confirmed therapeutic serum levels) for at least 2 weeks prior to study registration including any of the following:
Show all 54Show fewer
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Histologically confirmed grade IV astrocytoma (GBM), gliosarcoma, grade III astrocytoma, oligodendroglioma, or mixed oligoastrocytoma
  • All patients must have unequivocal evidence of tumor progression by MRI or CT scan performed no longer than 14 days prior to study registration
  • Patients undergoing surgery for progressive disease with nonmeasurable disease on post-operative MRI, ideally obtained within 48 hours of surgery, (i.e., macroscopic gross total resection) are eligible
  • ECOG performance status 0-2 (Karnofsky ≥ 60%)
  • Life expectancy > 3 months
  • Leukocytes ≥ 3,000/μL
  • Absolute neutrophil count ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 9 g/dL
  • Serum calcium ≤ 12.0 mg/dL
  • Total bilirubin within normal institutional limits (ULN)
  • AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN
  • Creatinine < 1.5 X institutional ULN
  • Patients must have QTc < 500 msec
  • The following groups of patients are eligible provided they have New York Heart Association class II cardiac function on baseline ECHO or MUGA:
  • Those with a history of class II heart failure who are asymptomatic on treatment
  • Those with prior anthracycline exposure
  • Those who have received central thoracic radiation that included the heart in the radiotherapy port
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation
  • All women of childbearing potential must have a negative pregnancy test prior to receiving sunitinib malate
  • Patients with a history of QTc prolongation (defined as a QTc interval >= 500 msec), serious ventricular arrhythmia (VT or VF > 3 beats in a row) or other significant ECG abnormalities are excluded
  • Patients with poorly controlled hypertension (systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg) are ineligible
  • Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow and retain sunitinib malate tablets are excluded
  • Patients with any of the following conditions are excluded:
  • Serious or non-healing wound, ulcer, or bone fracture
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment
  • History of myocardial infarction, cardiac arrhythmia, stable or unstable angina, symptomatic congestive heart failure, or coronary or peripheral artery bypass graft or stenting within 12 months prior to study entry
  • Class III or IV heart failure as defined by the NYHA functional classification system
  • Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infections requiring antibiotics or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
  • Pregnant women are excluded from this study
  • Breastfeeding should be discontinued if the mother is treated with sunitinib malate
  • Patients are eligible if they received up to 1 previous chemotherapy regimen
  • ≥ 12 weeks must have elapsed from the completion of radiation therapy
  • ≥ 4 weeks from previous non-nitrosoureas-based cytotoxic chemotherapy
  • ≥ 6 weeks from any nitrosoureas
  • ≥ 2 weeks from last cytostatic chemotherapy such as erlotinib hydrochloride or tamoxifen
  • Patients who have undergone previous stereotactic radiosurgery, intratumoral chemotherapy, or brachytherapy are eligible if functional imaging (PET or SPECT scan, MR spectroscopy, or dynamic MRI) supports the diagnosis of recurrent tumor or recurrent disease is confirmed histologically
  • Concurrent steroids allowed provided the patients is on a stable or decreasing dose for at least 7 days prior to baseline tumor assessment (MRI and/or CT scan)
  • Patients who have received prior treatment with any other antiangiogenic agent (e.g., bevacizumab, sorafenib, pazopanib, AZD2171, PTK787, or VEGF Trap) are ineligible
  • Patients who require use of therapeutic doses of coumarin-derivative anticoagulants such as warfarin or enoxaparin are excluded, although warfarin doses of up to 2 mg daily are permitted for prophylaxis of thrombosis
  • Low molecular weight heparin is permitted provided the patient's PT INR is < 1.5
  • Use of agents with proarrhythmic potential (e.g., terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, or flecainide) is not permitted during the study
  • No other investigational or commercial agents or non-investigational therapy designed to treat the brain malignancy (i.e., radiation therapy, systemic or intratumoral chemotherapy, biological agents, immunotherapy, or hormonal therapy) is allowed during the study period
  • HIV-positive patients on combination antiretroviral therapy are ineligible

Who cannot join

  • History of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate
  • Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiation therapy within 12 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • At least 4 weeks must have elapsed since any major surgery

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Pharmacokinetic and Phase 2 Study of Sunitinib Malate in Recurrent Malignant Gliomas

This phase II trial is studying how well sunitinib works in treating patients with recurrent malignant gliomas. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the efficacy of sunitinib malate in patients with recurrent malignant gliomas as measured by 6-month progression-free survival.

II. To determine the lower of the dose of sunitinib malate in patients receiving enzyme-inducing anti-convulsants that would achieve similar serum drug and metabolite concentrations as that in patients not receiving enzyme-inducing anticonvulsants or the maximum tolerated dose in the same population.

SECONDARY OBJECTIVES:

  1. To examine the toxicity and safety of sunitinib malate in patients with the above noted tumors.

II. To evaluate tumor responses in the stated patients. III. To evaluate progression-free and overall survival in the stated patients.

OUTLINE: This is a multicenter study. Patients are stratified according to use of enzyme-inducing anticonvulsants (EIAC) (yes vs no).

STRATUM 1 (non-EIAC): Patients receive oral sunitinib malate once daily for 4 consecutive weeks followed by 2 weeks of rest.

STRATUM 2 (EIAC \& OSU patients only): Patients receive oral sunitinib malate as in stratum 1. Patients receive escalating doses of oral sunitinib malate until the maximum tolerated dose (MTD) is determined.

Patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for plasma concentrations of sunitinib malate via LC/MS/MS method.

In both strata, treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

Being tested
sunitinib malate, pharmacological study
Medical subject headings
Astrocytoma, Glioblastoma, Gliosarcoma, Glioma, Oligodendroglioma

What participants receive

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

  • sunitinib malateDrug

    Also called SU11248, sunitinib, Sutent

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00499473
Study groupRoleWhat they receive
Stratum 1 (kinase inhibitor therapy)ExperimentalNon-EIAC patients receive oral sunitinib malate once daily for 4 consecutive weeks followed by 2 weeks of rest.
Receives: Drug: sunitinib malate; Other: pharmacological study
Stratum 2 (kinase inhibitor therapy)ExperimentalEIAC \& OSU patients receive oral sunitinib malate as in stratum 1. Patients receive escalating doses of oral sunitinib malate until the maximum tolerated dose (MTD) is determined.
Receives: Drug: sunitinib malate; Other: pharmacological study

What is being measured

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

  1. Progression-free Survival at 6 Months (Stratum 1)

    Number of patients with Progression-free Survival at 6 months for Stratum 1

    Measured: From time to registration to up to 6 months

  2. Maximum Tolerable Dose Based on Dose-limiting Toxicity of Sunitinib in Patients Receiving EIAC (Stratum 2)

    Maximum tolerable dose of sunitinib in patients receiving treatment with EIAC agents using dose escalation based on the steady-state trough sunitinib + SU12662 plasma concentrations on day 14 observed in patients treated in stratum 1. Six patients will be treated in each dose cohort with up to 12 patients being treated at the maximum tolerable dose for a total of 18-24 patients with gliomas receiving EIAC.

    Measured: From the time of first treatment with sunitinib until completion of treatment, assessed up to 30 days

  3. Dose Resulting in Steady-state Trough

    Average of pre-dose values of sunitinib + SU12662 plasma concentrations equivalent to that observed in patients not receiving EIAC based on pharmacokinetic modeling.

    Measured: At baseline (day 8) and days 15, 22, and 23

Secondary outcomes (3)

  1. Confirmed Objective Response (Complete Response[CR] or Partial Response [PR])

    Confirmatory scans should also be obtained within 4 to 6 weeks following initial documentation of objective response. Confidence intervals for the true proportion will be calculated using the exact binomial method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: up to 12 weeks

  2. Percentage of Patients Progression Free at 12 Months

    Measured: At 12 months after the start of treatment

  3. Overall Survival

    Measured: up to 12 months

Timeline

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

  1. First posted11 Jul 2007 (estimated)
  2. Study startJun 2007
  3. Primary completionJun 2009
  4. Study completionOct 2014

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
Parallel groups
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00499473
Sponsor's protocol ID
NCI-2009-00215
Other IDs
NCI-2009-00215, OSU-IRB-2006C0098, CDR0000554443, OSU-06060, OSU 06060, 7745, N01CM62207, N01CM62203
Status last verified
Jan 2016
First submitted
10 Jul 2007
Last updated
29 Feb 2016

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sunitinib malate and pharmacological study in people with Adult Anaplastic Astrocytoma and Adult Diffuse Astrocytoma, run by National Cancer Institute (NCI) 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 54 inclusion and 3 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 Feb 2016. 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 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?

Yes. Results are posted in the registry (first posted 29 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Progression-free Survival at 6 Months (Stratum 1) (time frame: From time to registration to up to 6 months). The study lists 3 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 NCT00499473.

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 Feb 2016.

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