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BIBW 2992 QTcF Trial in Patients With Relapsed or Refractory Solid Tumours
This study is currently recruiting participants.
Verified by Boehringer Ingelheim Pharmaceuticals, August 2009
First Received: April 2, 2009   Last Updated: August 20, 2009   History of Changes
Sponsored by: Boehringer Ingelheim Pharmaceuticals
Information provided by: Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00875433
  Purpose

A phase II trial to assess the impact of BIBW 2992 on the heart (QTcF) and the effectiveness of BIBW 2992 in treating certain cancers. Cancers studied will include glioblastoma and cancers which have spread to the brain (metastases).


Condition Intervention Phase
Neoplasms
Drug: BIBW 2992
Phase II

Study Type: Interventional
Study Design: Treatment, Single Group Assignment, Safety/Efficacy Study
Official Title: Phase II Open Label Trial to Assess the Efficacy and the Imapct on QTcF of Continuous Oral BIBW 2992 at a Daily Dose of 50mg in Patients With Relapsed or Refractory Solid Tumours Including Patients With Brain Metastases and Those With Glioblastoma Not Amenable to Other Therapy

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:
  • QTcF interval; Objective tumour response according to the Macdonald criteria for GBM patients and for patients with brain metastases, and the RECIST criteria for other patients. [ Time Frame: Four months ]

Secondary Outcome Measures:
  • Marked prolongation of QT; Cardiac safety parameters; Disease control rate (CR, PR, SD); Progression free survival (PFS); Molecular determinants of response; Incidence and intensity of adverse events; Pharmacokinetic characteristics of BIBW 2992 [ Time Frame: Four months ]

Estimated Enrollment: 60
Study Start Date: April 2009
Estimated Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
  Eligibility

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

Inclusion Criteria:

  1. Male or female patients aged at least 18 years old.
  2. Histologically or cytologically confirmed diagnosis of a solid malignant tumour, known to express EGFR/HER2 that is either refractory to standard therapies, or for which no standard treatment is available (including patients with brain metastases).
  3. At least one tumor lesion that can accurately be measured by computed tomography (CT) or magnetic resonance imaging (MRI) in at least one dimension with longest diameter to be recorded as greater than or equal to 20 mm using conventional techniques or greater than or equal to 10 mm with spiral CT scan.
  4. Life expectancy of at least 3 months.
  5. Written informed consent that is consistent with ICH-GCP guidelines.
  6. Eastern Cooperative Oncology Group (ECOG) performance score 0,1 or 2.
  7. Patients must have recovered from any previous surgery.
  8. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of trial participation. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days of trial enrolment. Breast feeding mothers will be excluded since these agents may be toxic to infants.

For patients with Glioma and brain metastases the following additional inclusion criteria should apply:

  1. Histologically-confirmed WHO Grade IV malignant glioma at first episode of recurrence after prior combined chemo-radiotherapy. Patients with prior low-grade glioma are eligible if histological assessment demonstrates transformation to WHO Grade IV malignant glioma.
  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).

Exclusion Criteria:

Major exclusion criteria;

  1. Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
  2. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks before first drug administration.
  3. Patients not completely recovered from any therapy-related toxicities from previous chemo-, hormone-, immuno-, or radiotherapies to CTC < Grade 1. Prior chemotherapy is allowed if completed at least 4 weeks prior to first trial treatment (6 weeks for mitomycin C or nitrosoureas) and the patient has recovered from the acute toxicities of that therapy.
  4. Prior treatment with EGFR targeting therapies or treatment with EGFR- or HER2 inhibiting drugs within the past four weeks before start of therapy or concomitantly with this trial.
  5. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3.
  6. Cardiac left ventricular function with resting ejection fraction < 50% measured by multigated blood pool imaging of the heart (MUGA scan) or Echocardiogram.
  7. QTcF- interval > 470 ms at screening.
  8. PR-interval > 230 ms at screening.
  9. QRS-interval >120 ms at screening.
  10. ST-segment and T/U-wave abnormalities at screening, as will be assessed by a cardiology specialist of a central lab.
  11. Absolute neutrophil count (ANC) < 1,500/mm3.
  12. Platelet count < 100,000 / mm3.
  13. Bilirubin > 1.5 mg / dl (>26 micro mol / L, SI unit equivalent). Aspartate amino transferase (AST) or alanine amino transferase (ALT) > or equal to three times the upper limit of normal (if related to liver metastases > five times the upper limit of normal).
  14. Serum creatinine > 1.5 times of the upper normal limit or calculated/measured creatinine clearance > or equal to 45 ml / min.

For Patients with glioma and brain metastases additional exclusion criteria apply;

  1. Patients with untreated or symptomatic brain metastases. Patients with treated, asymptomatic brain metastases are eligible if there has been no change in brain disease status for at least four (4) weeks, no history of cerebral oedema or bleeding in the past four (4) weeks. Steroids will be allowed. Anti-epileptic therapy will be allowed if no changes are anticipated within the initial 14 days of treatment (QTC-evaluation).
  2. Less than 4 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.
  3. Less than two weeks from surgical resection (one week from prior stereotactic biopsy) or major surgical procedure.
  4. Less than two weeks after previous chemotherapy (6 weeks from nitrosureas).
  5. Less than four weeks from prior treatment with bevacizumab.
  6. Treatment with other investigational drugs; participation in another clinical study within the past 2 weeks before start of therapy or concomitantly with this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00875433

Contacts
Contact: Boehringer Ingelheim Study Coordinator 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
United Kingdom
1200.24.4401 Boehringer Ingelheim Investigational Site Recruiting
Sutton, United Kingdom
1200.24.4402 Boehringer Ingelheim Investigational Site Recruiting
London, United Kingdom
1200.24.4403 Boehringer Ingelheim Investigational Site Recruiting
Guildford, United Kingdom
1200.24.4404 Boehringer Ingelheim Investigational Site Not yet recruiting
London, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim ( Boehringer Ingelheim, Study Chair )
Study ID Numbers: 1200.24
Study First Received: April 2, 2009
Last Updated: August 20, 2009
ClinicalTrials.gov Identifier: NCT00875433     History of Changes
Health Authority: Great Britain: MHRA;   United States: Food and Drug Administration

Study placed in the following topic categories:
Glioblastoma
Neoplasm Metastasis

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on September 11, 2009