Open Label Trial to Explore Safety of Combining Afatinib (BIBW 2992) and Radiotherapy With or Without Temozolomide in Newly Diagnosed Glioblastoma Multiform

NCT ID: NCT00977431

Last Updated: 2019-02-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-17

Study Completion Date

2017-09-12

Brief Summary

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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).

Detailed Description

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Conditions

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Glioblastoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Regimen U

BIBW2992 + Radiotherapy

Group Type EXPERIMENTAL

Radiotherapy

Intervention Type PROCEDURE

Day 1 to day 42

BIBW2992

Intervention Type DRUG

Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT

Regimen M

BIBW2992 + Temozolomide + Radiotherapy

Group Type EXPERIMENTAL

Temozolomide

Intervention Type DRUG

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

Intervention Type DRUG

Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT

Radiotherapy

Intervention Type PROCEDURE

Day 1 to day 42

Interventions

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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)

Intervention Type DRUG

Radiotherapy

Day 1 to day 42

Intervention Type PROCEDURE

BIBW2992

Escalating dose cohorts during Radiotherapy(RT) period, fixed dose after RT

Intervention Type DRUG

Radiotherapy

Day 1 to day 42

Intervention Type PROCEDURE

BIBW2992

Escalating dose cohorts during Radiotherapy(RT) period , fixed dose after RT

Intervention Type DRUG

Eligibility Criteria

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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. Karnofsky Performance Scale (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- Good Clinical Practice (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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

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Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Ninewells Hospital & Medical School

Dundee, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

The Christie Hospital

Manchester, , United Kingdom

Site Status

The Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Saran F, Welsh L, James A, McBain C, Gattamaneni R, Jefferies S, Harris F, Pemberton K, Schaible J, Bender S, Cseh A, Brada M. Afatinib and radiotherapy, with or without temozolomide, in patients with newly diagnosed glioblastoma: results of a phase I trial. J Neurooncol. 2021 Dec;155(3):307-317. doi: 10.1007/s11060-021-03877-6. Epub 2021 Nov 17.

Reference Type DERIVED
PMID: 34787778 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2008-007284-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1200.38

Identifier Type: -

Identifier Source: org_study_id

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