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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00727506
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Boehringer Ingelheim
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Boehringer Ingelheim
Principal Investigator Affiliation Boehringer Ingelheim
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Completed
Countries Canada, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioma
Arms & Interventions

Arms

Experimental: BIBW 2992

BIBW 2992 once daily

Active Comparator: TMZ

TMZ 21/28 days

Experimental: BIBW 2992 plus TMZ

BIBW 2992 once daily plus TMZ 21/28 days

Interventions

Drug: - BIBW 2992

BIBW 2992 once daily

Drug: - TMZ

TMZ 21/28

Drug: - BIBW 2992 plus TMZ

BIBW 2992 once daily plus TMZ 21/28 days

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Birmingham, Alabama

Status

Address

1200.36.0016 Boehringer Ingelheim Investigational Site

Birmingham, Alabama,

Phoenix, Arizona

Status

Address

1200.36.0012 Boehringer Ingelheim Investigational Site

Phoenix, Arizona,

Duarte, California

Status

Address

1200.36.0005 Boehringer Ingelheim Investigational Site

Duarte, California,

Los Angeles, California

Status

Address

1200.36.0014 Boehringer Ingelheim Investigational Site

Los Angeles, California,

Orlando, Florida

Status

Address

1200.36.0019 Boehringer Ingelheim Investigational Site

Orlando, Florida,

Atlanta, Georgia

Status

Address

1200.36.0023 Boehringer Ingelheim Investigational Site

Atlanta, Georgia,

Louisville, Kentucky

Status

Address

1200.36.0008 Boehringer Ingelheim Investigational Site

Louisville, Kentucky,

Boston, Massachusetts

Status

Address

1200.36.0002 Boehringer Ingelheim Investigational Site

Boston, Massachusetts,

Detroit, Michigan

Status

Address

1200.36.0003 Boehringer Ingelheim Investigational Site

Detroit, Michigan,

New York, New York

Status

Address

1200.36.0009 Boehringer Ingelheim Investigational Site

New York, New York,

Durham, North Carolina

Status

Address

1200.36.0001 Boehringer Ingelheim Investigational Site

Durham, North Carolina,

Charleston, South Carolina

Status

Address

1200.36.0007 Boehringer Ingelheim Investigational Site

Charleston, South Carolina,

Memphis, Tennessee

Status

Address

1200.36.0020 Boehringer Ingelheim Investigational Site

Memphis, Tennessee,

Dallas, Texas

Status

Address

1200.36.0017 Boehringer Ingelheim Investigational Site

Dallas, Texas,

Houston, Texas

Status

Address

1200.36.0010 Boehringer Ingelheim Investigational Site

Houston, Texas,

Charlottesville, Virginia

Status

Address

1200.36.0011 Boehringer Ingelheim Investigational Site

Charlottesville, Virginia,

Seattle, Washington

Status

Address

1200.36.0022 Boehringer Ingelheim Investigational Site

Seattle, Washington,

International Sites

Calgary, Alberta, Canada

Status

Address

1200.36.1005 Boehringer Ingelheim Investigational Site

Calgary, Alberta,

Winnipeg, Manitoba, Canada

Status

Address

1200.36.1010 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba,

Moncton, New Brunswick, Canada

Status

Address

1200.36.1009 Boehringer Ingelheim Investigational Site

Moncton, New Brunswick,

Halifax, Nova Scotia, Canada

Status

Address

1200.36.1011 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia,

Hamilton, Ontario, Canada

Status

Address

1200.36.1008 Boehringer Ingelheim Investigational Site

Hamilton, Ontario,

Kingston, Ontario, Canada

Status

Address

1200.36.1001 Boehringer Ingelheim Investigational Site

Kingston, Ontario,

Toronto, Ontario, Canada

Status

Address

1200.36.1003 Boehringer Ingelheim Investigational Site

Toronto, Ontario,

Toronto, Ontario, Canada

Status

Address

1200.36.1004 Boehringer Ingelheim Investigational Site

Toronto, Ontario,

Fleurimont, Quebec, Canada

Status

Address

1200.36.1007 Boehringer Ingelheim Investigational Site

Fleurimont, Quebec,

Montreal, Quebec, Canada

Status

Address

1200.36.1002 Boehringer Ingelheim Investigational Site

Montreal, Quebec,

Quebec, Canada

Status

Address

1200.36.1006 Boehringer Ingelheim Investigational Site

Quebec, ,