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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00727506
First received: July 31, 2008
Last updated: June 3, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Glioma
Drug: BIBW 2992
Drug: TMZ
Drug: BIBW 2992 plus TMZ
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of BIBW 2992 (Afatinib) in Treating Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Progression-free Survival (PFS-6) at Six Months - Phase II Part [ Time Frame: At six months after randomization ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Dose Limiting Toxicities - Phase I Part [ Time Frame: From randomization till data cut-off (10 Jun 2009), with a mean treatment duration of 51 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Tumor Response (OBR) in Phase II [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Objective Tumor Response (OBR) 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. ] [ Designated as safety issue: No ]
    OBR is defined as complete response (CR) and partial response (PR) according to the MacDonald criteria assessed by central independent review.


Enrollment: 151
Study Start Date: July 2008
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992
BIBW 2992 once daily
Drug: BIBW 2992
BIBW 2992 once daily
Active Comparator: TMZ
TMZ 21/28 days
Drug: TMZ
TMZ 21/28
Experimental: BIBW 2992 plus TMZ
BIBW 2992 once daily plus TMZ 21/28 days
Drug: BIBW 2992 plus TMZ
BIBW 2992 once daily plus TMZ 21/28 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00727506

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Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00727506     History of Changes
Other Study ID Numbers: 1200.36
Study First Received: July 31, 2008
Results First Received: August 8, 2013
Last Updated: June 3, 2014
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 28, 2014