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Adult Anaplastic AstrocytomaPhase 1/2NCT00045110

Erlotinib in Treating Patients With Recurrent Malignant Glioma or Recurrent or Progressive Meningioma

A Phase 1/2 study testing erlotinib hydrochloride, laboratory biomarker analysis and pharmacological study in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 7 sites 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

Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
erlotinib hydrochloride, laboratory biomarker analysis and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
136 participants
Where
7 sitesUnited States
Study dates
Aug 2002to Dec 2010
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

Who may be able to join

  • One of the following diagnoses:
  • Histologically confirmed intracranial malignant glioma
  • Glioblastoma multiforme (GBM), anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant astrocytoma not otherwise specified
  • Original histology of low-grade glioma allowed provided a subsequent histology of malignant glioma is confirmed
  • Histologically or radiographically confirmed recurrent or progressive benign or malignant meningioma
  • Progressive disease or tumor recurrence on MRI or CT scan
Show all 56Show fewer
  • Phase I: No more than 3 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
  • Phase II: No more than 2 prior relapses and no more than 2 prior chemotherapy* or biologic therapy regimens
  • Patients with progressive disease must have failed prior radiotherapy* that was completed at least 4 weeks ago
  • Patients with progressive disease between 4 and 12 weeks after completion of external beam radiotherapy must have clear evidence of progression on MRI
  • Patients with GBM who have completed external beam radiotherapy and do not show progression are eligible
  • Patients with progressive disease after interstitial brachytherapy or stereotactic radiosurgery must have confirmed true progression rather than radiation necrosis based upon positron-emission tomography, thallium scanning, MRI, or surgical documentation
  • Measurable or evaluable disease
  • Performance status - Karnofsky 60-100%
  • More than 8 weeks
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 mg/dL (transfusion allowed)
  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • SGOT less than 1.5 times ULN
  • Creatinine less than 1.5 mg/dL
  • None of the following ophthalmic abnormalities:
  • Abnormalities of the cornea (e.g., dry eye syndrome or Sjögren's syndrome)
  • Congenital abnormality (e.g., Fuch's dystrophy)
  • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
  • Abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Patients found to have dry eyes on examination but have an otherwise normal examination allowed
  • No active infection
  • No other serious concurrent medical illness
  • No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No other disease that would obscure toxicity or dangerously alter drug metabolism
  • No significant medical illness that would preclude study participation
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 12 weeks after study participation
  • See Disease Characteristics
  • At least 1 week since prior thalidomide
  • At least 1 week since prior interferon
  • At least 4 weeks since prior SU5416 or other experimental biologic agents
  • See Disease Characteristics
  • No prior chemotherapy (including polifeprosan 20 with carmustine implant [Gliadel wafers]) for patients with stable GBM
  • At least 2 weeks since prior vincristine
  • At least 3 weeks since prior procarbazine
  • At least 6 weeks since prior nitrosoureas
  • At least 1 week since prior tamoxifen
  • See Disease Characteristics
  • Recovered from prior radiotherapy
  • No more than 6 weeks since prior external beam radiotherapy for patients with GBM without evidence of progression
  • Recovered from prior surgery
  • Recovered from prior therapy
  • At least 1 week since prior noncytotoxic agents (e.g., isotretinoin) except radiosensitizers
  • At least 4 weeks since prior cytotoxic therapy
  • At least 4 weeks since prior tipifarnib or imatinib mesylate
  • No prior erlotinib or other epidermal growth factor receptor inhibitors
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Who cannot join

None listed.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • National Cancer Institute Neuro-Oncology Branch

    Bethesda, Maryland, 20814

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75235

  • University of California Los Angeles

    Los Angeles, California, 90095

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • University of California San Francisco

    San Francisco, California, 94115

Other trials in United States

About this study

Official title: A Phase I/II Trial of OSI-774 in Patients With Recurrent Malignant Gliomas and Malignant Gliomas Post Radiation Therapy

Phase I/II trial to study the effectiveness of erlotinib in treating patients who have recurrent malignant glioma or recurrent or progressive meningioma. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

Read the detailed description

OBJECTIVES:

Phase 1 I. Determine the maximum tolerated dose of erlotinib in patients with recurrent malignant glioma or recurrent or progressive meningioma.

II. Determine the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients.

Phase 2 I. Determine the 6-month progression-free survival (recurrent malignant glioma) II.12-month survival of patients treated with this drug (stable glioblastoma post radiation therapy)

Phase 2 - Secondary Recurrent Malignant Glioma I. Objective Tumor Response rate associated with erlotinib therapy in recurrent or progressive malignant glioma.

III. 12-month survival of patients treated with this drug Determine the safety profile of this drug in these patients. IV.. Determine the pharmacokinetics of this drug in these patients

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to study phase (I vs II), concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no), histology (recurrent GBM vs recurrent anaplastic glioma vs recurrent meningioma vs stable GBM), preoperative candidacy (yes vs no), and concurrent steroids (yes vs no).

Phase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

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

Phase II: Once the MTD is determined, additional patients concurrently receiving EIAEDs are treated with erlotinib as above at the phase II dose. Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose.

Patients are followed for survival.

Being tested
erlotinib hydrochloride, laboratory biomarker analysis, pharmacological study
Medical subject headings
Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Meningioma, Brain Neoplasms

What participants receive

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

  • erlotinib hydrochlorideDrug

    Also called CP-358,774, erlotinib, OSI-774

    given orally

  • laboratory biomarker analysisOther

    correlative studies

  • pharmacological studyOther

    correlative studies

Study groups in NCT00045110
Study groupRoleWhat they receive
Phase 1 Dose EscalationExperimentalPhase I: Patients concurrently receiving EIAEDs receive oral erlotinib once daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. erlotinib hydrochloride given orally Other: pharmacological study.
Receives: Drug: erlotinib hydrochloride; Other: pharmacological study
Phase 2 recurrent malignant gliomas and nonprogressive GBMExperimentalPhase II: Patients not concurrently receiving EIAEDs are treated with erlotinib as above at a predetermined dose (150mg/day. patients requiring surgery treated 7 days prior to tumor removal (150mg/day) PK analysis and effects of erlotinib on epidermal growth factor receptor (EGFR) erlotinib hydrochloride given orally Other: pharmacological study, laboratory biomarker analysis.
Receives: Drug: erlotinib hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

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

  1. Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I

    DLT Definition: any grade 3 thrombocytopenia and grade 4 anemia and neutropenia; any non-hematologic grade 3 toxicity; failure to recover from toxicities to be eligible for re-treatment with erlotinib within 2 weeks of the last dose of erlotinib.

    Measured: 28 days

  2. Define Maximum Tolerated Dose (MTD) of Erlotinib by Phase 1 Cohorts

    standard 3+3 dose escalation design 3 patients in each dose level, observed for 28 days before enrollment to next level. if none of the patients experienced DLT dose escalated, if 1 of 3 experienced DLT 3 more enrolled at that level, if none of the 3 additional pts had DLT escalate to next level, if one or more of the additional pts experienced DLT, the MTD was exceeded and 3 more patients were treated at the next lower dose (if only 3 pts treated at the lower dose). The MTD is the dose at which 0/3 or 1/6 patients have experienced a DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT.

    Measured: cycle 1 - 28 days

  3. 6 Months Progression-free Survival in Recurrent Malignant Gliomas (Phase II)

    Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

    Measured: 6 months

Secondary outcomes (15)

  1. Percent of Participants With a Grade 3 or 4 Adverse Events Phase 1

    CTCAE

    Measured: 1 year

  2. 1 Year Survival - Phase II Newly Diagnosed GBM Post RT

    12 month survival for newly diagnosed stable GBM post RT treated with erlotinib post RT

    Measured: At 1 year

  3. Overall Survival Newly Diagnosed GBM Post RT

    Overall Survival defined as Time from Start of treatment to time of death due to any cause

    Measured: 2 years

  4. Response Rate (Complete or Partial Response) Graded Using Modified RECIST Criteria Phase II

    Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI

    Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined.

    Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids.

    Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone.

    Stable/No Response: Does not qualify for CR, PR, or progression.

    Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over BL if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

    Measured: At 1 year

  5. Percent of Patients With One or More Grade 3-5 Toxicity Described Based on the CTC Severity Grading Phase II

    Summarized by descriptive statistics.

    Measured: Up to 1 year

  6. Time of Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1.

  7. Peak Plasma Concentration Per Dose Level Phase I (on Anticonvulsants) -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

  8. Estimation of the Area Under the Curve Per Dose Level Phase I (on Anticonvulsants) -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

  9. Trough Level Per Dose Level Phase I (on Anticonvulsants) -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: cycle 1 day eight

  10. Peak Plasma Concentration Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

  11. Time to Peak Plasma Concentration for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

  12. Estimation of Area Under the Curve for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg-

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: baseline, 1,2,4,6,8,12,24h post administration day 1 cycle 1. One sample on day 8 cycle 1 and day 1 of cycle 2,3 and 5

  13. Trough Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs - Phase 2 - Dose 150mg -

    plasma concentrations relative to erlotiniab administration and sample time and dose level

    Measured: One sample on day 8 cycle 1

  14. Pharmacokinetics (Plasma) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs

    Drug administered 6 days prior to surgery

    Measured: Pre-surgery and time of resection

  15. Pharmacokinetics (Tissue) Level for Recurrent Patients Not on Enzyme-inducing Antiepileptic Drugs

    Drug administered 6 days prior to surgery

    Measured: Pre-surgery and time of resection

Timeline

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

  1. First posted27 Jan 2003 (estimated)
  2. Study startAug 2002
  3. Primary completionDec 2010
  4. Study completionDec 2010

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
Parallel groups
Masking
None (open label)
Enrolment
136 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00045110
Sponsor's protocol ID
NCI-2012-02490
Other IDs
NCI-2012-02490, NCI-03-C-0114, CDR0000256358, NABTC-01-03, NABTC-01-03, U01CA062399
Status last verified
Jul 2017
First submitted
6 Sep 2002
Last updated
17 Aug 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Raizer JJ, Abrey LE, Lassman AB, Chang SM, Lamborn KR, Kuhn JG, Yung WK, Gilbert MR, Aldape KD, Wen PY, Fine HA, Mehta M, Deangelis LM, Lieberman F, Cloughesy TF, Robins HI, Dancey J, Prados MD; North American Brain Tumor Consortium. A phase I trial of erlotinib in patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meningiomas. Neuro Oncol. 2010 Jan;12(1):87-94. doi: 10.1093/neuonc/nop017. Epub 2009 Dec 14.

    PubMed 20150371

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing erlotinib hydrochloride, laboratory biomarker analysis and pharmacological study in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 7 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?

The sponsor lists 56 inclusion and 0 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 17 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 13 Jul 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?

Number of Dose Limiting Toxicity (DLT) Each Dose Level Phase I (time frame: 28 days). 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 NCT00045110, which also lists 1 linked publication.

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 17 Aug 2017.

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