Erlotinib Compared With Temozolomide or Carmustine in Treating Patients With Recurrent Glioblastoma Multiforme

July 26, 2017 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Randomized Phase II of TARCEVA™ (Erlotinib) Versus Temozolomide Or BCNU in Patients With Recurrent Glioblastoma Multiforme

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as temozolomide and carmustine, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether erlotinib is more effective than temozolomide or carmustine in treating recurrent glioblastoma multiforme.

PURPOSE: This randomized phase II trial is studying erlotinib to see how well it works compared to temozolomide or carmustine in treating patients with recurrent glioblastoma multiforme.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare the therapeutic activity of erlotinib vs temozolomide or carmustine in patients with recurrent glioblastoma multiforme.
  • Compare 6-month progression-free survival in patients treated with these drugs.

Secondary

  • Compare the safety of these drugs in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral erlotinib* once daily on day 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients treated with enzyme inducing anti-epileptic drugs (EIAEDs) receive a higher dose of erlotinib than patients not receiving any anti-epileptic drugs or EIAEDs.

  • Arm II: Patients who have not received prior temozolomide are assigned to receive temozolomide. Patients who have received prior temozolomide are assigned to receive carmustine. Patients receive 1 of the following treatment regimens:

    • Patients receive oral temozolomide* once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    • Patients receive carmustine IV once daily on days 1-3. Treatment repeats every 56 days for up to 5 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Chemotherapy-naïve patients receive a higher dose of temozolomide than patients who have received prior adjuvant chemotherapy.

Patients are followed every 8 weeks until disease progression and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 100-110 patients (50-55 per treatment arm) will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
  • France
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
      • Nantes-Saint Herblain, France, 44805
        • Centre Regional Rene Gauducheau
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 75651
        • CHU Pitié-Salpêtrière
      • Villejuif, France, F-94805
        • Institut Gustave Roussy
  • Italy
      • Padova, Italy, 35128
        • Azienda Ospedaliera di Padova
  • Netherlands
      • 's-Gravenhage, Netherlands, 2501 CK
        • Medisch Centrum Haaglanden
      • Rotterdam, Netherlands, 3000 CA
        • University Medical Center Rotterdam at Erasmus Medical Center
  • United Kingdom
    • Scotland
      • Glasgow, Scotland, United Kingdom, G11 6NT
        • Western Infirmary

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed glioblastoma multiforme

    • Some oligodendroglial elements allowed provided they make up < 25% of the tumor
  • Recurrent disease documented by MRI after prior radiotherapy
  • At least 1 bidimensionally measurable target lesion ≥ 2 cm by MRI

  • Undergone prior surgery for recurrent primary brain tumor more than 3 months before study entry

    • Must have a clearly limited target lesion ≥ 2 cm OR evidence of progressive and measurable target lesion OR a second measurable target lesion outside the surgical area

PATIENT CHARACTERISTICS:

Age

  • Over 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm ^3

Hepatic

  • AST and ALT < 2.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN

Renal

  • Creatinine < 1.5 times ULN

Cardiovascular

  • Clinically normal cardiac function
  • No ischemic heart disease within the past 12 months
  • No New York Heart Association grade III or IV cardiac insufficiency
  • No unstable angina
  • No arryhthmia

Pulmonary

  • DLCO > 70% of predicted (for patients randomized to receive erlotinib [arm I] or carmustine [arm II])

  • No history of pulmonary disease that would affect pulmonary function including any of the following:

    • Chronic bronchopneumopathy
    • Pleural effusion
    • Interstitial pnuemonia
    • Pulmonary lymphangitis

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No other malignancy except cone biopsied carcinoma of the cervix or adequately treated basal cell or squamous cell skin cancer
  • No psychological, familial, sociological, or geographical factors that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior HER-targeted agents
  • No concurrent growth factors for neutrophil count elevation
  • No concurrent epoetin alfa

Chemotherapy

  • Prior adjuvant temozolomide allowed
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • No more than 1 prior adjuvant chemotherapy regimen
  • No prior chemotherapy for recurrent disease

Endocrine therapy

  • Must be on a stable or decreasing dose of corticosteroids for at least 2 weeks before study entry

Radiotherapy

  • See Disease Characteristics
  • More than 3 months since prior radiotherapy to the brain
  • No prior high-dose radiotherapy (> 65 Gy), stereotactic radiosurgery, or internal radiotherapy unless disease recurrence confirmed

Surgery

  • See Disease Characteristics

Other

  • No prior participation in experimental therapies
  • No concurrent CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, troleandomycin, cimetidine, or grapefruit juice)

  • No concurrent warfarin or other coumarin derivatives

    • Concurrent low-molecular weight heparin allowed
  • No other concurrent investigational drugs

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free survival at 6 months

Secondary Outcome Measures

Outcome Measure
Response (complete [CR] or partial response [PR]) measured by McDonald's criteria at least 4 weeks after first documented response and every 8 weeks until disease progression or until start of another treatment
Severe toxic events assessed by CTCAE v3.0 at the end of each course
Progression-free survival at 1 year
Overall survival at 6 months and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

March 1, 2006

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

July 8, 2004

First Submitted That Met QC Criteria

July 9, 2004

First Posted (Estimate)

July 12, 2004

Study Record Updates

Last Update Posted (Actual)

July 27, 2017

Last Update Submitted That Met QC Criteria

July 26, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-26034-16031

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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