Overview

This trial is active, not recruiting.

Condition glioma
Treatments bibw 2992, tmz, bibw 2992 plus tmz
Phase phase 2
Target EGFR
Sponsor Boehringer Ingelheim
Start date July 2008
End date January 2011
Trial size 151 participants
Trial identifier NCT00727506, 1200.36

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
BIBW 2992 once daily
bibw 2992
BIBW 2992 once daily
(Active Comparator)
TMZ 21/28 days
tmz
TMZ 21/28
(Experimental)
BIBW 2992 once daily plus TMZ 21/28 days
bibw 2992 plus tmz
BIBW 2992 once daily plus TMZ 21/28 days

Primary Outcomes

Measure
Progression-free Survival (PFS-6) at Six Months - Phase II Part
time frame: At six months after randomization
Number of Participants With Dose Limiting Toxicities - Phase I Part
time frame: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days

Secondary Outcomes

Measure
Objective Tumor Response (OBR) in Phase II
time frame: From randomization to until the date of first documented progression or data cutoff on May 12, 2011, whichever came first, with a mean treatment duration of 91 days
Objective Tumor Response (OBR) in Phase I
time frame: From treatment start until the date of first documented progression or data cutoff at May 12, 2011, whichever came first, with a mean treatment duration of 69.7 days.

Eligibility Criteria

Male or female participants at least 18 years old.

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).

Additional Information

Official title Phase I/II Trial of BIBW 2992 (Afatinib) in Treating Patients With Recurrent Glioblastoma Multiforme
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Boehringer Ingelheim.