Phase 1
N=36
Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform
Glioblastoma
Bottom Line
View on ClinicalTrials.gov: NCT00977431 ↗Enrolled (actual)
36
Serious AEs
66.7%
Results posted
Feb 2019
Primary outcome: Primary: Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase — 1; 0; 2; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Temozolomide (Drug); Radiotherapy (Procedure); BIBW2992 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Boehringer Ingelheim
- Primary completion
- Sep 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Investigator Defined Dose Limiting Toxicities (DLT) During the RT Phase |
1; 0; 2; 0; 1 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Afatinib |
30; 40 | — |
| SECONDARY Incidence and Intensity of Adverse Events (AE) According to Common Terminology Criteria of Adverse Events (CTCAE v.3.0) |
0; 0; 1; 0; 1; 0 | — |
| SECONDARY The Objective Tumour Response According to the Macdonald Criteria |
5; 3; 5; 3; 10; 2 | — |
| SECONDARY Concentration of Afatinib in Plasma at Steady State Pre-dose on Days 8, 15 and 29 |
4.4; 10.7; 15.7; 4.9; 16.7; 5.6 | — |
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) O6-methylguanine-DNA methyltransferase gene (MGMT) to treat newly diagnosed patients with Grade IV Glioblastoma (primary brain cancer).
Eligibility Criteria
Inclusion criteria
- Histologically-confirmed WHO Grade IV newly diagnosed malignant glioma.
- Proven MGMT gene promoter methylation status
- 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.
- Age more or equal to 18 years and less than 70 years at entry
- Karnofsky Performance Scale (KPS) more or equal to 70%
- Patients receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before start of treatment.
- Written informed consent that is consistent with local law and ICH- Good Clinical Practice (GCP) guidelines.
Exclusion criteria
- Less than two weeks from surgical resection or other major surgical procedure at start of treatment.
- Planned surgery for other diseases
- Placement of Gliadel® wafer at surgery.
- Prior or planned radiotherapy of the cranium including brachytherapy and/or radiosurgery for GBM.
- 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.
- 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 diarrhoea.
- Patients with known pre-existing interstitial lung disease
- Serious illness or concomitant non-oncological disease considered by the investigator to be incompatible with the protocol.
- 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.
- Cardiac left ventricular function with resting ejection fraction less than 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 or suspected active drug or alcohol abuse.
- Known hypersensitivity to BIBW 2992 or the excipients of any of the trial drugs.
Data sourced from ClinicalTrials.gov (NCT00977431). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.