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

Glioma Clinical Trial

Official title:

Phase I/II Trial of BIBW 2992 (Afatinib) in Treating Patients With Recurrent Glioblastoma Multiforme

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00727506
• Other study ID #: 1200.36
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 31, 2008
• Last updated: March 21, 2016
• Start date: July 2008
• Est. completion date: March 2016

Study information

• Verified date: March 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 151
• Est. completion date: March 2016
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioma

Intervention

Drug:
• BIBW 2992
BIBW 2992 once daily
• TMZ
TMZ 21/28
• BIBW 2992 plus TMZ
BIBW 2992 once daily plus TMZ 21/28 days

Locations

Country	Name	City	State
Canada	1200.36.1005 Boehringer Ingelheim Investigational Site	Calgary	Alberta
Canada	1200.36.1007 Boehringer Ingelheim Investigational Site	Fleurimont	Quebec
Canada	1200.36.1011 Boehringer Ingelheim Investigational Site	Halifax	Nova Scotia
Canada	1200.36.1008 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1200.36.1001 Boehringer Ingelheim Investigational Site	Kingston	Ontario
Canada	1200.36.1009 Boehringer Ingelheim Investigational Site	Moncton	New Brunswick
Canada	1200.36.1002 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1200.36.1006 Boehringer Ingelheim Investigational Site	Quebec
Canada	1200.36.1003 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1200.36.1004 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1200.36.1010 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
United States	1200.36.0023 Boehringer Ingelheim Investigational Site	Atlanta	Georgia
United States	1200.36.0016 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	1200.36.0002 Boehringer Ingelheim Investigational Site	Boston	Massachusetts
United States	1200.36.0007 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	1200.36.0017 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1200.36.0003 Boehringer Ingelheim Investigational Site	Detroit	Michigan
United States	1200.36.0005 Boehringer Ingelheim Investigational Site	Duarte	California
United States	1200.36.0001 Boehringer Ingelheim Investigational Site	Durham	North Carolina
United States	1200.36.0010 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1200.36.0014 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	1200.36.0020 Boehringer Ingelheim Investigational Site	Memphis	Tennessee
United States	1200.36.0009 Boehringer Ingelheim Investigational Site	New York	New York
United States	1200.36.0019 Boehringer Ingelheim Investigational Site	Orlando	Florida
United States	1200.36.0012 Boehringer Ingelheim Investigational Site	Phoenix	Arizona
United States	1200.36.0022 Boehringer Ingelheim Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS-6) at Six Months - Phase II Part	PFS-6 is defined as probability of patients surviving to six months after randomization without progression. Disease progression was evaluated by an independent review committee and by the investigators, independently. The evaluation by the independent review committee was used for the primary outcome measure. The measurement "Number" the estimated PFS-6 value from the Kaplan-Meier curve of PFS.	At six months after randomization	No
Primary	Number of Participants With Dose Limiting Toxicities - Phase I Part		From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days	No
Secondary	Objective Tumor Response (OBR) in Phase II	OBR is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review. Only data collected until cut-off date May 12, 2011 were considered.	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	No
Secondary	Objective Tumor Response (OBR) in Phase I	OBR is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review.	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.	No