Overview

This trial is active, not recruiting.

Condition glioblastoma
Treatments temozolomide, radiotherapy, bibw2992
Phase phase 1
Sponsor Boehringer Ingelheim
Start date September 2009
End date October 2016
Trial size 36 participants
Trial identifier NCT00977431, 1200.38, 2008-007284-17

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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
BIBW2992 + Radiotherapy
radiotherapy
Day 1 to day 42
bibw2992
Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT
(Experimental)
BIBW2992 + Temozolomide + Radiotherapy
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)
bibw2992
Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT
radiotherapy
Day 1 to day 42

Primary Outcomes

Measure
MTD of BIBW 2992 when given concomitantly with Temozolomide (TMZ) and radiotherapy
time frame: 6 weeks
Maximum Tolerated Dose (MTD) of BIBW 2992 when given concomitantly with radiotherapy
time frame: 6 weeks

Secondary Outcomes

Measure
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
Objective tumour response according to the Macdonald criteria
time frame: Until disease progression or undue side effect
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

Male or female participants from 18 years up to 69 years old.

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.

Additional Information

Official title Phase I, Open Label Trial to Explore Safety of Combining BIBW 2992 and Radiotherapy With or Without Temozolomide in Newly Diagnosed GBM
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.