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Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform

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ClinicalTrials.gov Identifier: NCT00977431
Recruitment Status : Completed
First Posted : September 15, 2009
Last Update Posted : September 18, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

This study is a phase I, open label trial to determine the Maximum Tolerated Dose (MTD), safety, pharmacokinetics, and efficacy of BIBW 2992 (an epidermal growth factor receptor(EGFR)inhibitor) to be used in combination with:

  • radiotherapy alone (in patients with an unmethylated (functioning) MGMT gene regulator) or
  • radiotherapy and Temozolomide (in patients with a methylated (silenced) MGMT gene) to treat newly diagnosed patients with Grade IV Glioblastoma (primary brain cancer).

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: Temozolomide Procedure: Radiotherapy Drug: BIBW2992 Phase 1

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open Label Trial to Explore Safety of Combining BIBW 2992 and Radiotherapy With or Without Temozolomide in Newly Diagnosed GBM
Actual Study Start Date : September 17, 2009
Primary Completion Date : September 12, 2017
Study Completion Date : September 12, 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Regimen U
BIBW2992 + Radiotherapy
Procedure: Radiotherapy
Day 1 to day 42
Drug: BIBW2992
Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT
Experimental: Regimen M
BIBW2992 + Temozolomide + Radiotherapy
Drug: Temozolomide
During RT: 75 mg/m2 daily , 4 weeks after RT: given days 1 to 5 of 28 day cycles (150 mg/m2 in cycle 1, 200 mg/m2 in cycle 2 up to cycle 6)
Drug: BIBW2992
Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT
Procedure: Radiotherapy
Day 1 to day 42

Outcome Measures

Primary Outcome Measures :
  1. MTD of BIBW 2992 when given concomitantly with Temozolomide (TMZ) and radiotherapy [ Time Frame: 6 weeks ]
  2. Maximum Tolerated Dose (MTD) of BIBW 2992 when given concomitantly with radiotherapy [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Safety of BIBW 2992: Incidence and intensity of AEs according to Common Terminology Criteria (CTCAE v.3.0) [ Time Frame: Until disease progression or undue side effect ]
  2. Objective tumour response according to the Macdonald criteria [ Time Frame: Until disease progression or undue side effect ]
  3. Pharmacokinetics of BIBW 2992 in combination with radiotherapy (RT) with or without concomitant Temozolomide therapy [ Time Frame: day 8, day 15, day 29 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Histologically-confirmed WHO Grade IV newly diagnosed malignant glioma.
  2. Proven MGMT gene promoter methylation status
  3. Available early postoperative Gd-enhanced MRI (within 72 hours after initial surgery). In case a patient did not perform a Gd-enhanced MRI within 72 hours post surgery, a Gd-MRI is to be performed prior to start of study treatment.
  4. Age more or equal to 18 years and less than 70 years at entry
  5. KPS more or equal to 70%
  6. Patients receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before start of treatment.
  7. Written informed consent that is consistent with local law and ICH-GCP guidelines.

Exclusion criteria:

  1. Less than two weeks from surgical resection or other major surgical procedure at start of treatment.
  2. Planned surgery for other diseases
  3. Placement of Gliadel® wafer at surgery.
  4. Prior or planned radiotherapy of the cranium including brachytherapy and/or radiosurgery for GBM.
  5. Treatment with other investigational drugs; participation in another clinical study including exposure to the investigational product within the past 4 weeks before start of therapy or concomitantly with this study.
  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 diarrhoea.
  9. Patients with known pre-existing interstitial lung disease
  10. Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
  11. Patient is less than 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.
  12. Cardiac left ventricular function with resting ejection fraction less than 50%.
  13. Absolute neutrophil count (ANC) less than 1500/mm3.
  14. Platelet count less than 100,000/mm3.
  15. Bilirubin greater than 1.5 x upper limit of institutional norm.
  16. Aspartate amino transferase (AST) greater than 3 x upper limit of institutional norm.
  17. Serum creatinine greater than 1.5 x upper limit of institutional norm.
  18. Patients who are sexually active and unwilling to use a medically acceptable method of contraception.
  19. Pregnancy or breast-feeding.
  20. Patients unable to comply with the protocol.
  21. Known or suspected active drug or alcohol abuse.
  22. Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00977431

United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Ninewells Hospital & Medical School
Dundee, United Kingdom, DD1 9SY
The Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom, G12 0YN
The Christie Hospital
Manchester, United Kingdom, M20 4BX
The Royal Marsden Hospital
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
More Information

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00977431     History of Changes
Other Study ID Numbers: 1200.38
2008-007284-17 ( EudraCT Number )
First Posted: September 15, 2009    Key Record Dates
Last Update Posted: September 18, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents