GliomaPhase 2NCT00727506
BIBW 2992 (Afatinib) With or Without Daily Temozolomide in the Treatment of Patients With Recurrent Malignant Glioma
A Phase 2 study testing BIBW 2992, TMZ and BIBW 2992 plus TMZ in people with Glioma, run by Boehringer Ingelheim at 28 sites in 2 countries.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- BIBW 2992, TMZ and BIBW 2992 plus TMZ
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 28 sitesin 2 countries
- Study dates
- 14 Jul 2008to 25 May 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Phase I Part:
- 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.
- Age at least 18 years at entry
- KPS at least 60%
- Patients must have recovered from previous surgery and chemotherapy.
- Written informed consent that is consistent with local law and ICH-GCP guidelines.
Show all 14Show fewer
- Phase II Part:
- 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.
- 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).
- Age at least 18 years at entry
- KPS at least 70%
- Patients must have recovered from previous surgery and chemotherapy.
- Written informed consent that is consistent with local law and ICH-GCP guidelines.
- Patients receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before start of study treatment.
Who cannot join
- Phase I and Phase II Parts:
- 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.
- Less than two weeks from surgical resection (one week from prior stereotactic biopsy) or major surgical procedure.
- Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
- Treatment with other investigational drugs; participation in another clinical study within the past 2 weeks before start of therapy or concomitantly with this study.
- Progressive disease or toxicity =CTCAEv3 Grade 3 to protracted temozolomide dosing (defined as temozolomide administered more than 5 days/28 day cycle).
Show all 28Show fewer
- Active infectious disease requiring intravenous therapy.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Gastrointestinal disorders that may interfere with the absorption of the study drug or chronic diarrhea.
- Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
- 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.
- Cardiac left ventricular function with resting ejection fraction <50%.
- Absolute neutrophil count (ANC) less than 1500/mm3.
- Platelet count less than 100,000/mm3.
- Bilirubin greater than 1.5 x upper limit of institutional norm.
- Aspartate amino transferase (AST) greater than 3 x upper limit of institutional norm.
- Serum creatinine greater than 1.5 x upper limit of institutional norm.
- Patients who are sexually active and unwilling to use a medically acceptable method of contraception.
- Pregnancy or breast-feeding.
- Patients unable to comply with the protocol.
- 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:
- Prior EGFR-directed therapy.
- Prior bevacizumab therapy.
- Patients presenting with second or higher number of episodes of recurrence.
- Requirement of treatment with any of the prohibited concomitant medications listed in Section 4.2.2 (Restrictions regarding concomitant treatment).
Trial locations and contacts
28 sites in 2 countries.
28 sites in 2 countries
United States17 sites
1200.36.0023 Boehringer Ingelheim Investigational Site
Atlanta, Georgia
1200.36.0016 Boehringer Ingelheim Investigational Site
Birmingham, Alabama
1200.36.0002 Boehringer Ingelheim Investigational Site
Boston, Massachusetts
1200.36.0007 Boehringer Ingelheim Investigational Site
Charleston, South Carolina
1200.36.0011 Boehringer Ingelheim Investigational Site
Charlottesville, Virginia
1200.36.0017 Boehringer Ingelheim Investigational Site
Dallas, Texas
1200.36.0003 Boehringer Ingelheim Investigational Site
Detroit, Michigan
1200.36.0005 Boehringer Ingelheim Investigational Site
Duarte, California
1200.36.0001 Boehringer Ingelheim Investigational Site
Durham, North Carolina
1200.36.0010 Boehringer Ingelheim Investigational Site
Houston, Texas
1200.36.0014 Boehringer Ingelheim Investigational Site
Los Angeles, California
1200.36.0008 Boehringer Ingelheim Investigational Site
Louisville, Kentucky
1200.36.0020 Boehringer Ingelheim Investigational Site
Memphis, Tennessee
1200.36.0009 Boehringer Ingelheim Investigational Site
New York, New York
1200.36.0019 Boehringer Ingelheim Investigational Site
Orlando, Florida
1200.36.0012 Boehringer Ingelheim Investigational Site
Phoenix, Arizona
1200.36.0022 Boehringer Ingelheim Investigational Site
Seattle, Washington
Canada11 sites
1200.36.1005 Boehringer Ingelheim Investigational Site
Calgary, Alberta
1200.36.1007 Boehringer Ingelheim Investigational Site
Fleurimont, Quebec
1200.36.1011 Boehringer Ingelheim Investigational Site
Halifax, Nova Scotia
1200.36.1008 Boehringer Ingelheim Investigational Site
Hamilton, Ontario
1200.36.1001 Boehringer Ingelheim Investigational Site
Kingston, Ontario
1200.36.1009 Boehringer Ingelheim Investigational Site
Moncton, New Brunswick
1200.36.1002 Boehringer Ingelheim Investigational Site
Montreal, Quebec
1200.36.1006 Boehringer Ingelheim Investigational Site
Québec, Quebec
1200.36.1003 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1200.36.1004 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1200.36.1010 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba
About this study
Official title: Phase I/II Trial of BIBW 2992 (Afatinib) in Treating Patients With Recurrent Glioblastoma Multiforme
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.
- Conditions
- Glioma
- Being tested
- BIBW 2992, TMZ, BIBW 2992 plus TMZ
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIBW 2992Drug
BIBW 2992 once daily
TMZDrug
TMZ 21/28
BIBW 2992 plus TMZDrug
BIBW 2992 once daily plus TMZ 21/28 days
| Study group | Role | What they receive |
|---|---|---|
| BIBW 2992 | Experimental | BIBW 2992 once daily Receives: Drug: BIBW 2992 |
| TMZ | Active comparator | TMZ 21/28 days Receives: Drug: TMZ |
| BIBW 2992 plus TMZ | Experimental | BIBW 2992 once daily plus TMZ 21/28 days Receives: Drug: BIBW 2992 plus TMZ |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With DLT- Phase I
Number of Participants With Dose Limiting Toxicities (DLT) - Phase I Part
Measured: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days
Progression-free Survival (PFS-6) at Six Months - Phase II
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.
Measured: At six months after randomization
Secondary outcomes (29)
Objective Tumor Response in Phase I
Objective Tumor Response is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review.
Measured: 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.
Objective Tumor Response in Phase II
Objective Tumor Response 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 July 15, 2016 were considered.
Measured: From randomization to until the date of first documented progression or data cutoff on July 15, 2016, whichever came first, with a mean treatment duration of 110.0 days
Progression-free Survival (PFS)- Phase II Part
Progression-free survival was defined as the duration between randomization and the date of the first of the two following events: progression or death.
Measured: from date of randomization until the date of first documented progression or death by any cause, whichever came first, assessed up to 9 Months.
AUCτ,ss for Afatinib
Area under the plasma concentration-time curve of afatinib after multiple administration (AUCτ,ss) of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide (TMZ).
Measured: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24 h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
Cmax,ss for Afatinib
maximum measured plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide.
Measured: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
Tmax,ss for Afatinib
time from dosing to the maximum plasma concentration of afatinib after multiple administration of 50 mg afatinib in presence and absence of 75 mg/m² temozolomide
Measured: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
AUC (0-8) for Temozolomide
Area under the plasma concentration-time curve over the time interval from zero to 08h (AUC (0-8)) of temozolomide in presence and absence of afatinib.
Measured: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Cmax for Temozolomide
maximum measured plasma concentration following the first dose of uniform intervals τ (Cmax) of temozolomide in presence and absence of afatinib.
Measured: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Tmax for Temozolomide
time from dosing to the maximum plasma concentration following the first dose of uniform intervals τ (tmax) of temozolomide in presence and absence of afatinib.
Measured: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
t1/2 for Temozolomide
terminal half-life (t1/2) of temozolomide in presence and absence of afatinib
Measured: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Phase II - Trough Plasma Concentration of Afatinib
Trough plasma concentration of afatinib after multiple administration of 40 mg afatinib administered as monotherapy or in combination with 75 mg/m² temozolomide
Measured: Before (-0.05 h) the drug administration of afatinib on Day 15 of Cycle 2 & 3
Number of Participants With EGFRvIII Assessed by IHC Test.
Number of participants with the epidermal growth factor receptor variant III (EGFRvIII) assessed by IHC test for the evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFRvIII by immunohistochemistry (IHC) test.
Measured: Baseline (during screening)
Number of Participants With MGMT Marker Assessed by IHC Test.
Number of participants with MGMT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for O6-methylguanine-DNA methyltransferase (MGMT) by immunohistochemistry (IHC) test.
Measured: Baseline (during screening)
Number of Participants With EGFR Marker Assessed by IHC Test.
Number of participants with EGFR marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry (IHC) test
Measured: Baseline (during screening)
Number of Participants With PTEN Marker Assessed by IHC Test.
Number of participants with PTEN marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Phosphatase and Tensin Homologue - a tumor suppressor gene/protein (PTEN) by immunohistochemistry (IHC) test.
Measured: Baseline (during screening)
Number of Participants With PAKT Marker Assessed by IHC Test.
Number of participants with PAKT marker assessed by IHC test for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Serinethreonine kinase (PAKT) by immunohistochemistry (IHC) test.
Measured: Baseline (during screening)
Number of Participants With EGFR Assessed by FISH
Number of participants with EGFR assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for EGFR by fluorescent in situ hybridization (FISH).
Measured: Baseline (during screening)
Number of Participants With PTEN Assessed by FISH
Number of participants with PTEN assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for PTEN by fluorescent in situ hybridization (FISH).
Measured: Baseline (during screening)
Number of Participants With Chromosomes (CEP7) Assessed by FISH
Number of participants with Chromosomes (CEP7) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP7) by fluorescent in situ hybridization (FISH).
Measured: Baseline (during screening)
Number of Participants With Chromosomes (CEP10) Assessed by FISH
Number of participants with Chromosomes (CEP10) assessed by FISH for evaluation of molecular determinants of response to afatinib. Archival tumor samples from enrolled patients were collected and analyzed for Chromosomes (CEP10) by fluorescent in situ hybridization (FISH).
Measured: Baseline (during screening)
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
Safety was assessed based on number of participants with investigator defined drug-related AEs, AEs leading to discontinuation of trial drug, All Serious Adverse events (AE) and other significant AEs (according to International Conference on Harmonisation (ICH) E3).
Measured: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological
Measured: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Safety of Afatinib assesed based on Number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Measured: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Causes of Death - Phase I
Cause of the death reported during on treatment was due to disease progression.
Measured: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
Safety was assessed based on number of participants with investigator defined drug-related AEs, AE leading to dose reduction, Adverse events (AEs) leading to discontinuation of trial drug and All Serious Adverse events (SAE).
Measured: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Safety of afatinib as indicated by number of participants with adverse events based on intensity and incidence of AE's, especially skin reactions (rash, acne), gastrointestinal (GI) (Vomiting, nausea, diarrhea) and neurological.
Measured: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Safety of Afatinib assessed based on the number of participants with adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Measured: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Causes of Death - Phase II
Causes of death during on treatment.
Measured: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Clinically Relevant Abnormalities for Decreased Cardiac Left Ventricular Function - Phase II
Number of participants with Clinically Relevant Abnormalities for decreased Cardiac left ventricular function.
Measured: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2008 (estimated)
- Study start14 Jul 2008
- Primary completion12 May 2011
- Study completion25 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 151 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00727506
- Sponsor's protocol ID
- 1200.36
- Status last verified
- Jul 2017
- First submitted
- 31 Jul 2008
- Last updated
- 15 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of BIBW 2992 (Afatinib) in Treating Patients With Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00727506
- Acronym / sponsor ID
- 1200.36
- Conditions
- Glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 151 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 14 Jul 2008 (actual)
- Primary completion
- 12 May 2011 (actual)
- Study completion
- 25 May 2016 (actual)
- First posted
- 4 Aug 2008 (estimated)
- Results
- Posted 24 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BIBW 2992 | Experimental | Drug: BIBW 2992BIBW 2992 once daily |
| TMZ | Active comparator | Drug: TMZTMZ 21/28 days |
| BIBW 2992 plus TMZ | Experimental | Drug: BIBW 2992 plus TMZBIBW 2992 once daily plus TMZ 21/28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
- Age at least 18 years at entry
- KPS at least 60%
- Patients must have recovered from previous surgery and chemotherapy.
- Written informed consent that is consistent with local law and ICH-GCP guidelines.
Key exclusion criteria (28 listed)
- 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.
- Less than two weeks from surgical resection (one week from prior stereotactic biopsy) or major surgical procedure.
- Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
- Treatment with other investigational drugs; participation in another clinical study within the past 2 weeks before start of therapy or concomitantly with this study.
- Progressive disease or toxicity =CTCAEv3 Grade 3 to protracted temozolomide dosing (defined as temozolomide administered more than 5 days/28 day cycle).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIBW 2992BIBW 2992 once daily | Drug | BIBW 2992 |
| TMZTMZ 21/28 | Drug | TMZ |
| BIBW 2992 plus TMZBIBW 2992 once daily plus TMZ 21/28 days | Drug | BIBW 2992 plus TMZ |
Primary outcome
Number of Participants With DLT- Phase I
Time frame: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days
Number of Participants With Dose Limiting Toxicities (DLT) - Phase I Part
Progression-free Survival (PFS-6) at Six Months - Phase II
Time frame: At six months after randomization
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.
29 secondary outcomes
Objective Tumor Response 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.
Objective Tumor Response in Phase II
Time frame: From randomization to until the date of first documented progression or data cutoff on July 15, 2016, whichever came first, with a mean treatment duration of 110.0 days
Progression-free Survival (PFS)- Phase II Part
Time frame: from date of randomization until the date of first documented progression or death by any cause, whichever came first, assessed up to 9 Months.
AUCτ,ss for Afatinib
Time frame: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24 h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
Cmax,ss for Afatinib
Time frame: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
Tmax,ss for Afatinib
Time frame: Before (-0.05 h) the drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h and 24h after drug administration on Day 15 (in presence of temozolomide) and Day 28 (in absence of temozolomide) of treatment Cycle 1
AUC (0-8) for Temozolomide
Time frame: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Cmax for Temozolomide
Time frame: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Tmax for Temozolomide
Time frame: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
t1/2 for Temozolomide
Time frame: Before (-0.05 h) the first drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8 h after drug administration on Day 1 (in absence of afatinib) and Day 15 (in presence of afatinib) of treatment Cycle 1
Phase II - Trough Plasma Concentration of Afatinib
Time frame: Before (-0.05 h) the drug administration of afatinib on Day 15 of Cycle 2 & 3
Number of Participants With EGFRvIII Assessed by IHC Test.
Time frame: Baseline (during screening)
Number of Participants With MGMT Marker Assessed by IHC Test.
Time frame: Baseline (during screening)
Number of Participants With EGFR Marker Assessed by IHC Test.
Time frame: Baseline (during screening)
Number of Participants With PTEN Marker Assessed by IHC Test.
Time frame: Baseline (during screening)
Number of Participants With PAKT Marker Assessed by IHC Test.
Time frame: Baseline (during screening)
Number of Participants With EGFR Assessed by FISH
Time frame: Baseline (during screening)
Number of Participants With PTEN Assessed by FISH
Time frame: Baseline (during screening)
Number of Participants With Chromosomes (CEP7) Assessed by FISH
Time frame: Baseline (during screening)
Number of Participants With Chromosomes (CEP10) Assessed by FISH
Time frame: Baseline (during screening)
Number of Participants With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, All Serious Adverse Events (AE) and Other Significant AEs - Phase I
Time frame: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase I
Time frame: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Adverse Events, Graded According CTCAE - Phase I
Time frame: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Causes of Death - Phase I
Time frame: From first administration of treatment until 28 days after last drug administration, up to 491 days.
Number of Participants With Investigator Defined Drug-Related AEs, AE Leading to Dose Reduction, AEs Leading to Discontinuation of Trial Drug and All SAE- Phase II
Time frame: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Adverse Events (AEs) Based on Intensity and Incidence of AE's - Phase II
Time frame: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Adverse Events, Graded According CTCAE - Phase II
Time frame: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Causes of Death - Phase II
Time frame: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Number of Participants With Clinically Relevant Abnormalities for Decreased Cardiac Left Ventricular Function - Phase II
Time frame: From first administration of treatment until 28 days after last drug administration, up to 518 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
28 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BIBW 2992, TMZ and BIBW 2992 plus TMZ in people with Glioma, run by Boehringer Ingelheim at 28 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With DLT- Phase I (time frame: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2017; AzTrials last refreshed its copy on 7 Nov 2026.