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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00977431
First received: September 14, 2009
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Glioblastoma
Drug: Temozolomide
Procedure: Radiotherapy
Drug: BIBW2992
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • MTD of BIBW 2992 when given concomitantly with Temozolomide (TMZ) and radiotherapy [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Maximum Tolerated Dose (MTD) of BIBW 2992 when given concomitantly with radiotherapy [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Objective tumour response according to the Macdonald criteria [ Time Frame: Until disease progression or undue side effect ] [ Designated as safety issue: No ]
  • Pharmacokinetics of BIBW 2992 in combination with radiotherapy (RT) with or without concomitant Temozolomide therapy [ Time Frame: day 8, day 15, day 29 ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: September 2009
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00977431

Locations
United Kingdom
1200.38.4402 Boehringer Ingelheim Investigational Site
Cambridge, United Kingdom
1200.38.4405 Boehringer Ingelheim Investigational Site
Dundee, United Kingdom
1200.38.4404 Boehringer Ingelheim Investigational Site
Glasgow, United Kingdom
1200.38.4403 Boehringer Ingelheim Investigational Site
Manchester, United Kingdom
1200.38.4401 Boehringer Ingelheim Investigational Site
Sutton, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00977431     History of Changes
Other Study ID Numbers: 1200.38, 2008-007284-17
Study First Received: September 14, 2009
Last Updated: April 2, 2014
Health Authority: Great Britain: EMEA

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014