BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma

NCT ID: NCT00727506

Last Updated: 2017-08-15

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

151 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-14

Study Completion Date

2016-05-25

Brief Summary

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Phase I Part: To determine the maximum tolerated dose (MTD) and pharmacokinetics of BIBW 2992 administered in combination with TMZ in patients with recurrent malignant gliomas (WHO Grade III and IV).

Phase II Part: To estimate the efficacy and safety of BIBW 2992 monotherapy and BIBW 2992 / TMZ combination therapy compared to TMZ monotherapy (three treatment arms) in patients with recurrent GBM. To evaluate molecular determinants of response to BIBW 2992.

Detailed Description

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Conditions

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Glioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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BIBW 2992

BIBW 2992 once daily

Group Type EXPERIMENTAL

BIBW 2992

Intervention Type DRUG

BIBW 2992 once daily

TMZ

TMZ 21/28 days

Group Type ACTIVE_COMPARATOR

TMZ

Intervention Type DRUG

TMZ 21/28

BIBW 2992 plus TMZ

BIBW 2992 once daily plus TMZ 21/28 days

Group Type EXPERIMENTAL

BIBW 2992 plus TMZ

Intervention Type DRUG

BIBW 2992 once daily plus TMZ 21/28 days

Interventions

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BIBW 2992

BIBW 2992 once daily

Intervention Type DRUG

TMZ

TMZ 21/28

Intervention Type DRUG

BIBW 2992 plus TMZ

BIBW 2992 once daily plus TMZ 21/28 days

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Phase I Part:

1. Histologically-confirmed WHO Grade III or IV malignant glioma that is recurrent after prior chemoradiotherapy. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO Grade III or IV malignant glioma.
2. Age at least 18 years at entry
3. KPS at least 60%
4. Patients must have recovered from previous surgery and chemotherapy.
5. Written informed consent that is consistent with local law and ICH-GCP guidelines.

Phase II Part:

1. Histologically-confirmed WHO Grade IV malignant glioma at first episode of recurrence after prior combined chemoradiotherapy. Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to WHO Grade IV malignant glioma and if prior treatment included temozolomide chemotherapy and radiotherapy.
2. Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on Gd MRI performed within 14 days prior to first treatment (Day 1).
3. Age at least 18 years at entry
4. KPS at least 70%
5. Patients must have recovered from previous surgery and chemotherapy.
6. Written informed consent that is consistent with local law and ICH-GCP guidelines.
7. Patients receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before start of study treatment.

Exclusion Criteria

Phase I and Phase II Parts:

1. Less than 12 weeks between radiotherapy and start of study treatment, unless new enhancing lesion outside of radiation field or radiologically progressive on two consecutive MRI scans at least four weeks apart or biopsy-proven recurrence.
2. Less than two weeks from surgical resection (one week from prior stereotactic biopsy) or major surgical procedure.
3. Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
4. Treatment with other investigational drugs; participation in another clinical study within the past 2 weeks before start of therapy or concomitantly with this study.
5. Progressive disease or toxicity =CTCAEv3 Grade 3 to protracted temozolomide dosing (defined as temozolomide administered more than 5 days/28 day cycle).
6. Active infectious disease requiring intravenous therapy.
7. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
8. Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.
9. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
10. Patient is \<3 years free of another primary malignancy except: if the other primary malignancy is either not currently clinically significant or does not require active intervention (such as a basal cell skin cancer or a cervical carcinoma in situ). Existence of any other malignant disease is not allowed.
11. Cardiac left ventricular function with resting ejection fraction \<50%.
12. Absolute neutrophil count (ANC) less than 1500/mm3.
13. Platelet count less than 100,000/mm3.
14. Bilirubin greater than 1.5 x upper limit of institutional norm.
15. Aspartate amino transferase (AST) greater than 3 x upper limit of institutional norm.
16. Serum creatinine greater than 1.5 x upper limit of institutional norm.
17. Patients who are sexually active and unwilling to use a medically acceptable method of contraception.
18. Pregnancy or breast-feeding.
19. Patients unable to comply with the protocol.
20. Known pre-existing interstitial lung disease (ILD).

Phase I part only:

1\. Less than four weeks from prior treatment with bevacizumab.

Phase II Part only:

1. Prior EGFR-directed therapy.
2. Prior bevacizumab therapy.
3. Patients presenting with second or higher number of episodes of recurrence.
4. Requirement of treatment with any of the prohibited concomitant medications listed in Section 4.2.2 (Restrictions regarding concomitant treatment).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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1200.36.0016 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Site Status

1200.36.0012 Boehringer Ingelheim Investigational Site

Phoenix, Arizona, United States

Site Status

1200.36.0005 Boehringer Ingelheim Investigational Site

Duarte, California, United States

Site Status

1200.36.0014 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Site Status

1200.36.0019 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Site Status

1200.36.0023 Boehringer Ingelheim Investigational Site

Atlanta, Georgia, United States

Site Status

1200.36.0008 Boehringer Ingelheim Investigational Site

Louisville, Kentucky, United States

Site Status

1200.36.0002 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

Site Status

1200.36.0003 Boehringer Ingelheim Investigational Site

Detroit, Michigan, United States

Site Status

1200.36.0009 Boehringer Ingelheim Investigational Site

New York, New York, United States

Site Status

1200.36.0001 Boehringer Ingelheim Investigational Site

Durham, North Carolina, United States

Site Status

1200.36.0007 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Site Status

1200.36.0020 Boehringer Ingelheim Investigational Site

Memphis, Tennessee, United States

Site Status

1200.36.0017 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Site Status

1200.36.0010 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Site Status

1200.36.0011 Boehringer Ingelheim Investigational Site

Charlottesville, Virginia, United States

Site Status

1200.36.0022 Boehringer Ingelheim Investigational Site

Seattle, Washington, United States

Site Status

1200.36.1005 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Site Status

1200.36.1010 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba, Canada

Site Status

1200.36.1009 Boehringer Ingelheim Investigational Site

Moncton, New Brunswick, Canada

Site Status

1200.36.1011 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

Site Status

1200.36.1008 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Site Status

1200.36.1001 Boehringer Ingelheim Investigational Site

Kingston, Ontario, Canada

Site Status

1200.36.1003 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Site Status

1200.36.1004 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Site Status

1200.36.1007 Boehringer Ingelheim Investigational Site

Fleurimont, Quebec, Canada

Site Status

1200.36.1002 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Site Status

1200.36.1006 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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1200.36

Identifier Type: -

Identifier Source: org_study_id

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