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Adult Brain TumorPhase 1/2NCT00379080

Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma

A Phase 1/2 study testing conventional surgery, tandutinib and pharmacological study in people with Adult Brain Tumor and Adult Giant Cell Glioblastoma, run by National Cancer Institute (NCI) at 9 sites in United States.

Completed

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

Official record
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Trial summary

This phase I/II trial is studying the side effects and best dose of tandutinib and to see how well it works in treating patients with recurrent or progressive glioblastoma.Tandutinib 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?
conventional surgery, tandutinib and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
9 sitesUnited States
Study dates
Jan 2007to Jun 2013
Phase
Phase 1/2
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

Criteria:

  • Histologically confirmed glioblastoma:
  • Progressive or recurrent disease after prior radiotherapy (with or without chemotherapy)
  • Patients with a previous low-grade glioma that progressed after prior radiotherapy (with or without chemotherapy) and are found to have glioblastoma by biopsy are eligible
  • Measurable disease, defined as contrast-enhancing progressive or recurrent glioblastoma by MRI or CT imaging within the past 2 weeks
  • Must be maintained on a stable corticosteroid regimen from the time of baseline scan to the start of study treatment
  • Feasibility study only:
  • Planning to undergo surgical resection or biopsy
  • Stereotactic biopsy for confirmation of tumor progression or differentiation of tumor progression from treatment-induced effects allowed
  • Corticosteroids must be tapered to the lowest required steroid dose and patient must be maintained on a stable dose after surgery or biopsy
  • Karnofsky performance status 60-100%
  • Absolute neutrophil count >= 1,500/mm^3
  • Hemoglobin >= 10 mg/dL
  • Bilirubin =< 1.5 mg/dL
  • AST and ALT =< 4 times upper limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment
  • Mini Mental State Exam score >= 15
  • Mean QTc =< 500 msec (with Bazett's correction) by screening electrocardiogram
  • LVEF >= 40%
  • No history of familial long QT syndrome
  • No myocardial infarction within the past 6 months
  • No severe uncontrolled ventricular arrhythmias
  • No uncontrolled angina
  • No electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • No ongoing vomiting or nausea >= grade 2
  • No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous alimentation
  • No active peptic ulcer disease
  • No other condition that would impair ability to swallow pills or absorb oral medications
  • No muscular dystrophy
  • No myasthenia gravis
  • No other known or suspected primary muscular or neuromuscular disease
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tandutinib (e.g., erlotinib hydrochloride, gefetinib, or doxazosin mesylate)
  • Patients who developed an acneiform/maculopustular rash while receiving either gefitinib or erlotinib hydrochloride are eligible unless the rash is considered an allergic reaction (angioedema/urticaria) or Stevens-Johnson syndrome
  • No ongoing or active infections
  • No psychiatric illness or social situations that would preclude study compliance
  • No other serious infection or medical illness
  • At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • No other uncontrolled illness
  • No other malignancy within the past 5 years except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • Recovered from prior therapy
  • At least 3 months since prior radiotherapy
  • No prior surgical procedures affecting absorption
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No concurrent agent that would cause QTc prolongation
  • No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
  • At least 10 days since prior and no concurrent anticonvulsant drugs that induce hepatic metabolic enzymes (e.g., primidone, oxcarbazepine, phenytoin, carbamazepine, or phenobarbital)
  • No prior treatment with small molecule inhibitors of platelet-derived growth factor receptor (e.g., sunitinib malate, sorafenib, or imatinib mesylate)
  • Platelet count >= 100,000/mm^3
  • No New York Heart Association class III or IV heart failure
  • Creatinine =< 1.5 mg/dL OR creatinine clearance >= 60mL/min

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma

This phase I/II trial is studying the side effects and best dose of tandutinib and to see how well it works in treating patients with recurrent or progressive glioblastoma.Tandutinib 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. Assess the ability of tandutinib to achieve a target tumor/plasma ratio ≥ 0.33 in patients with recurrent glioblastoma undergoing resection. (Feasibility study) II. Detect potential biological effects of tandutinib by measuring platelet-derived growth factor receptor phosphorylation status and downstream activation of Akt and Erk. (Feasibility study) III. Determine the maximum tolerated dose of tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) IV. Estimate the frequency of toxicities associated with tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) V. Describe the pharmacokinetics of this route of administration in patients with recurrent or progressive glioblastoma. (Phase I) VI. Assess tumor response rate in patients with recurrent or progressive glioblastoma. (Phase II)

SECONDARY OBJECTIVES:

  1. Estimate overall survival of patients with recurrent or progressive glioblastoma. (Phase II) II. Estimate the 6-month progression-free survival rate in these patients. (Phase II) III. Assess the toxicities associated with tandutinib in these patients. (Phase II) IV. Assess the pharmacokinetic profile of this route of administration in these patients. (Phase II) V. Explore protein-expression patterns that distinguish patients who respond to therapy from those who do not. (Phase II)

OUTLINE: This is a multicenter, prospective, nonrandomized, feasibility study and phase I study (in parallel) followed by an open label phase II study.

FEASIBILITY STUDY: Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

[Note: *On day 1 of course 1, patients receive only 1 dose of tandutinib.]

PHASE II: Patients receive tandutinib as in phase I at the MTD determined in phase I.

Patients undergo blood sample collection for pharmacokinetic studies. Patients in the feasibility portion of the study also undergo blood and tissue sample collection for correlative studies by mass spectrometry for tandutinib concentration. Samples are also examined for circulating endothelial cells and plasma proteins (vascular endothelial growth factor [VEGF]-A, -B, -C, and -D, soluble VEGF receptors [sVEGFR's], placental growth factor [P1GF], platelet-derived growth factor [PDGF]-AA, PDGF-AB, PDGF-BB, angiopoietin-1 and -2, tumstatin, thrombospondin-1, and IL-8) as potential markers of the antiangiogenic effect of tandutinib.

After completion of study treatment, patients are followed every 2 months.

Being tested
conventional surgery, tandutinib, pharmacological study, Tissue samples
Medical subject headings
Brain Neoplasms, Glioblastoma, Gliosarcoma

What participants receive

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

Study groups in NCT00379080
Study groupRoleWhat they receive
Arm I - FeasibilityExperimentalPatients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surgery, patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. conventional surgery oral tandutinib Pharmacological study Tissue samples
Receives: Procedure: conventional surgery; Drug: tandutinib; Other: pharmacological study; Other: Tissue samples
Arm 2 - Dose Escalation (Phase 1)ExperimentalPhase I: Patients receive oral tandutinib twice daily* on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tandutinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD. the starting dose for tandtinib is 500mg BID oral tandutinib Pharmacological study Tissue samples
Receives: Drug: tandutinib; Other: pharmacological study; Other: Tissue samples
Arm 3 - Phase 2ExperimentalPatients receive tandutinib as in phase I at the MTD determined in phase I. 600mg was the determined MTD in Dose Escalation oral tandutinib Pharmacological study Tissue samples
Receives: Drug: tandutinib; Other: pharmacological study; Other: Tissue samples

What is being measured

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

  1. Maximum Tolerated Dose of Tandutinib Defined by Dose Limiting Toxicities (Phase 1)

    Measured: cycle 1 - 28 days

  2. To Determine the Tumor/Plasma Ratio of in Subjects With Recurrent GBM Undergoing Resections (Phase 0)

    participants are administered tandutinib (500mg BID) for 7 days prior to surgery and then undergo resection for recurrent glioblastoma. Tissue samples will be collected for correlative studies - determine tumor/plasma ratio.

    Measured: 7 days prior to surgery including surgery

  3. Number of Dose Limiting Toxicities Per Dose Level

    cohorts of 3-6 pts will recieve oral tandutinib starting at 500mg BID with a dose escalation in each cohort. Each treatment cycle is 28 days. Evaluation period for MTD is 1st cycle - 28 days.

    dose limiting toxicity defined as: grades 3-4 severity (except vomiting and diarrhea without sufficient prophylaxis delay of treatment > 14 days. ANC less/equal 500m/mm3; Plts less/equal 25,000/mm3; febrile neutropenia or delay of treatment > 14 days

    Measured: 28 days

  4. Tumor Response (Complete Response and Partial Response) Rate (Phase II)

    pts receive a scan baseline and prior to every odd cycle. All responses are centrally reviewed Complete response Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response Greater than or equal 50% reduction in tumor size on MRI, on sable or decreasing glucocorticoids with stable or improving neurological exam for a minimum of 4 wks.

    Progressive disease Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.

    Stable disease Clinical status and MRI does not qualify for complete response, partial response or progression

    Measured: Up to 4 years

  5. Pharmacokinetics (Max Concentration of Plasma) for Tandutinib in Phase 1 and Phase 2

    pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2

    Measured: 28 days

  6. Pharmacokinetics (Apparent Terminal Phase Half-life) for Tandutinib in Phase 1 and Phase 2

    pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2

    Measured: 28 days

  7. Pharmacokinetics (Area Under the Plasma Concentration Time Profile From Zero to Infinity (AUC)) for Tandutinib in Phase 1 and Phase 2

    pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2

    Measured: 28 days

  8. Pharmacokinetics; Apparent Oral Clearance for Tandutinib in Phase 1 and Phase 2

    pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2

    Measured: 28 days

  9. Pharmacokinetics; Apparent Oral Total Body Volume of Distribution for Tandutinib in Phase 1 and Phase 2

    pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2

    Measured: 28 days

  10. Pharmacokinetics; Steady-state Trough Concentration for Tandutinib in Phase 1 and Phase 2

    pre-dose, 1,2,4,6,8 and 24 hrs post dose and days 8,15, 21 of cycle 1 and day one of cycle 2

    Measured: 28 days

Secondary outcomes (5)

  1. Overall Survival (Phase II)

    Median time of survival along with 95% confidence interval will be estimated using Kaplan-Meier method. An overall failure rate will be estimated with 95% CI.

    Measured: Up to 4 years

  2. Six-month Progression-free Survival Rate (Phase II)

    The probability of 6-momth progression-free survival will be estimated using binomial distribution.

    Progression defined as: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.

    Measured: At 6 months

  3. Overall Failure Rate (Phase II)

    The overall failure rate is expressed as hazard of failure per person-year of follow-up.

    Measured: up to 4 years

  4. Proportion of Patients With Serious or Life Threatening Toxicities

    Grade 3 or 4 toxicities related to treatment as determined by the CTCAE

    Measured: 2 year period

  5. Protein Expression Patterns Post Treatment - Loss or Gain

    serial blood samples over multiple time points (prior to treatment, 2 days post treatment, 8 days post treatment, 10 days post treatment and 28 days post treatment.

    statistical analyses presented for the comparisons that yielded a p-value <=0.05

    Measured: baseline - cycle 2 (28 days)

Timeline

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

  1. First posted21 Sep 2006 (estimated)
  2. Study startJan 2007
  3. Primary completionSep 2012
  4. Study completionJun 2013

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00379080
Sponsor's protocol ID
NCI-2009-00681
Other IDs
NCI-2009-00681, CDR0000495253, NABTT 0504, NABTT-0504, U01CA137443
Status last verified
Feb 2017
First submitted
19 Sep 2006
Last updated
7 Apr 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing conventional surgery, tandutinib and pharmacological study in people with Adult Brain Tumor and Adult Giant Cell Glioblastoma, run by National Cancer Institute (NCI) at 9 sites 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?

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 7 Apr 2017. 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. 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 combined 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.

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 7 Apr 2017). 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?

Maximum Tolerated Dose of Tandutinib Defined by Dose Limiting Toxicities (Phase 1) (time frame: cycle 1 - 28 days). The study lists 10 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 NCT00379080.

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 7 Apr 2017; AzTrials last refreshed its copy on 8 Nov 2026.

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