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

NCT00727506 | Completed Phase 2 Results

• 1 other identifier: 1200.36
• Study Type: interventional
• Target: 151
• Locations: 2 countries
• Sites: 28

Brief 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.

Conditions

Glioma

Outcome Measures

Primary Outcomes (2)

• Number of Participants With DLT- Phase I

  Number of Participants With Dose Limiting Toxicities (DLT) - Phase I Part

  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.

  At six months after randomization

Secondary Outcomes (29)

• Objective Tumor Response in Phase I

  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

  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

  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

  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

  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

Study Arms (3)

BIBW 2992

EXPERIMENTAL

BIBW 2992 once daily

Drug: BIBW 2992

TMZ

ACTIVE COMPARATOR

TMZ 21/28 days

Drug: TMZ

BIBW 2992 plus TMZ

EXPERIMENTAL

BIBW 2992 once daily plus TMZ 21/28 days

Drug: BIBW 2992 plus TMZ

Interventions

BIBW 2992 DRUG

BIBW 2992 once daily

BIBW 2992

TMZ DRUG

TMZ 21/28

TMZ

BIBW 2992 plus TMZ DRUG

BIBW 2992 once daily plus TMZ 21/28 days

BIBW 2992 plus TMZ

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (28)

1200.36.0016 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

Location

1200.36.0012 Boehringer Ingelheim Investigational Site

Phoenix, Arizona, United States

Location

1200.36.0005 Boehringer Ingelheim Investigational Site

Duarte, California, United States

Location

1200.36.0014 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

Location

1200.36.0019 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

1200.36.0023 Boehringer Ingelheim Investigational Site

Atlanta, Georgia, United States

Location

1200.36.0008 Boehringer Ingelheim Investigational Site

Louisville, Kentucky, United States

Location

1200.36.0002 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

Location

1200.36.0003 Boehringer Ingelheim Investigational Site

Detroit, Michigan, United States

Location

1200.36.0009 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1200.36.0001 Boehringer Ingelheim Investigational Site

Durham, North Carolina, United States

Location

1200.36.0007 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

1200.36.0020 Boehringer Ingelheim Investigational Site

Memphis, Tennessee, United States

Location

1200.36.0017 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

Location

1200.36.0010 Boehringer Ingelheim Investigational Site

Houston, Texas, United States

Location

1200.36.0011 Boehringer Ingelheim Investigational Site

Charlottesville, Virginia, United States

Location

1200.36.0022 Boehringer Ingelheim Investigational Site

Seattle, Washington, United States

Location

1200.36.1005 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

1200.36.1010 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba, Canada

Location

1200.36.1009 Boehringer Ingelheim Investigational Site

Moncton, New Brunswick, Canada

Location

1200.36.1011 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

Location

1200.36.1008 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1200.36.1001 Boehringer Ingelheim Investigational Site

Kingston, Ontario, Canada

Location

1200.36.1003 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1200.36.1004 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1200.36.1007 Boehringer Ingelheim Investigational Site

Fleurimont, Quebec, Canada

Location

1200.36.1002 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

Location

1200.36.1006 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

Location

MeSH Terms

Conditions

Glioma

Interventions

Afatinib; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2008
• First Posted: August 4, 2008
• Study Start: July 14, 2008
• Primary Completion: May 12, 2011
• Study Completion: May 25, 2016
• Last Updated: August 15, 2017
• Results First Posted: January 24, 2014

Record last verified: 2017-07

Locations

US (17); CA (11)