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Phase II Trial of BIBW 2992 (Afatinib) in Genetically Pre-screened Cancers With EGFR and/or HER2 Gene Amplification.

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ClinicalTrials.gov Identifier: NCT00748709
Recruitment Status : Terminated
First Posted : September 9, 2008
Results First Posted : October 14, 2013
Last Update Posted : November 28, 2013
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Description
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Brief Summary:
This is a Phase II open-label exploratory trial of BIBW 2992 administered to patients with tumors of various histologies found to possess EGFR and/or HER2 gene amplification, or EGFR activating mutations.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: BIBW 2992 (Afatinib) Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase II Trial of BIBW 2992 (Afatinib) in Genetically Pre-screened Cancers With EGFR and/or HER2 Gene Amplification or EFGR Activating Mutations.
Study Start Date : October 2008
Actual Primary Completion Date : November 2010

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Arms and Interventions
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Arm Intervention/treatment
Experimental: BIBW 2992 (Afatinib)
BIBW 2992 (Afatinib) for patients FISH positive for/or harboring EGFR or HER2 Mutation
 Drug: BIBW 2992 (Afatinib)
BIBW 2992 (Afatininb) for patients FISH positive for/or harboring EGFR or HER2 Mutation


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Objective Response (OR) [ Time Frame: Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks thereafter ]
    OR is defined as the percentage of patients with complete response (CR) or partial response (PR) and was assessed according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST 1.0).


Secondary Outcome Measures :
  1. Percentage of Participants With Clinical Benefit (CB) [ Time Frame: Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock ]
    CB was defined as CR, PR or stable disease (SD) and was assessed according to RECIST 1.0 criteria.

  2. Time to Objective Response (OR) [ Time Frame: Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock ]
    The time to OR was the duration from the first treatment to the time when the measurement criteria for CR and/or PR were met according to RECIST 1.0 criteria.

  3. Duration of OR [ Time Frame: Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock. ]
    Duration of OR was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death was objectively documented.

  4. Progression-free Survival (PFS) [ Time Frame: Tumour assessments were performed at screening, week 6, week 12, and every 8 weeks till database lock. ]
    PFS was defined as the time from the start of treatment to the occurrence of disease progression or death, whichever came first. Disease progression was assessed according to RECIST 1.0 criteria as well as by the investigators assessment, progression date recorded from post trial follow up or start of new anticancer treatment.

  5. Patients With AEs Resulting in Dose Reduction or Treatment Discontinuation [ Time Frame: First administration of trial medication until 28 days after last administration of trial medication ]
    Patients with adverse events (AEs) resulting in dose reduction or treatment discontinuation

  6. Maximum CTCAE Grade [ Time Frame: First administration of trial medication until 28 days after last administration of trial medication ]
    Patients with AEs by maximum Common Terminology Criteria for Adverse Events (CTCAE) grade

  7. Pre-dose Concentration of Afatinib in Plasma at Steady State on Day 15 (Cpre,ss,15) for Patients on 50mg on Day 15 [ Time Frame: Day 15 ]
    Cpre,ss,15 represents the pre-dose concentration of afatinib in plasma at steady state on day 15 for patients on 50mg on day 15.

  8. Number of Patients With Diarrhea or Rash [ Time Frame: First administration of trial medication until 28 days after last administration of trial medication ]
    Number of Patients with Diarrhea or Rash


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

There are 2 Steps in the screening process:

Step 1 Inclusion criteria for pre-screening:

  1. Histologically confirmed diagnosis of advanced cancer of one of the following four tumor type categories:

    Category 1, Gastric, GE junction, or Esophageal cancer Category 2, Biliary or gallbladder cancer Category 3, TCC urothelial tract, and Category 4, Gynecological cancers

  2. Measurable disease by RECIST criteria.
  3. Willingness and ability to give written informed consents consistent with ICHGCP guidelines.
  4. Life expectancy of at least three (3) months.
  5. Eastern Cooperative Oncology Group performance score 0, 1 or 2.
  6. Age >18 years.

Step 2 Inclusion criteria for enrollment:

Patients who have tested positive for FISH and are considered candidate for this trial must meet all of the following inclusion criteria:

  1. Histologically confirmed diagnosis of advanced cancer of one of the following four tumor type categories:

    Category 1, Gastric, GE junction, or Esophageal cancer Category 2, Biliary or gallbladder cancer Category 3, TCC urothelial tract, and Category 4, Gynecological cancers

  2. Documented failure to respond or progression of underlying cancer after at least one line of prior chemotherapy.
  3. EGFR and/or HER2 gene amplification by FISH testing or patients with tumors that harbor known activating EGFR mutations.
  4. Measurable disease by RECIST criteria.
  5. Willingness and ability to give written informed consents consistent with ICH-GCP guidelines.
  6. Life expectancy of at least three (3) months.
  7. Eastern Cooperative Oncology Group performance score 0, 1 or 2.
  8. Age >18 years.

Exclusion criteria:

  1. Prior treatment with gefitinib, erlotinib, lapatinib and/or other EGFR TKIs.
  2. Treatment with cytotoxic anti-cancer-therapies or investigational drugs during the last four weeks prior to the first treatment with the trial drug. (a shorter duration may be considered for patients treated with oral, non cytotoxic drugs on an individual basis and upon discussion between the principal investigator and sponsor)
  3. Inability to take BIBW 2992 by mouth (BIBW 2992 may not be crushed or administered via Gastrostomy-tube)
  4. Chronic diarrhea or other gastrointestinal disorders that may interfere with the absorption of the trial drug.
  5. History of other malignancies unless free of disease for at least 3 years (except for appropriately treated superficial non-melanoma skin cancer and surgically cured cervical cancer in situ).
  6. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of 3, unstable angina or poorly controlled arrhythmia. Myocardial infarction within 6 months prior to randomization.
  7. Resting left ventricular ejection fraction <50% OR below the institution's lower limit of normal (if the institutions lower limit is above 50%), measured by MUGA scan or echocardiogram.
  8. Active infectious disease
  9. Serious illness, concomitant non-oncological disease or mental problems considered by the investigator to be incompatible with participation in this trial.
  10. Active/symptomatic brain metastases. Patients with a history of treated brain metastases must have stable or normal brain MRI scan at screening and be at least three months post-radiation or surgery for brain metastasis.
  11. Absolute Neutrophil Count (ANC) less than 1,000/mm3.
  12. Platelet count less than 100,000/mm3.
  13. Hemoglobin Level less than 9.0 grams/dl.
  14. Total Bilirubin greater than 1.5 mg/dl; higher Total Bilirubin values may be acceptable for patients with known Gilbert¿s disease, approval by the PI and sponsor will be necessary.
  15. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal; or 5 times the upper limit of normal in patients with neoplastic liver involvement.
  16. Serum creatinine greater than 1.5 x upper limit of normal for the institution.
  17. Patients who are sexually active and unwilling to use simultaneously two medically acceptable method of contraception, one of which being a barrier type method such as condom.
  18. Pregnancy or breast-feeding.
  19. Patients unable to comply with the protocol
  20. Active alcohol and/or substance abuse.
  21. Continuation of therapy-related toxicities from prior anti cancer therapies, prior surgery, of CTCAE Grade >=2 at the time of the first administration of the trial drug.
  22. Patients with known pre-existing interstitial lung disease.
  23. Requirement for treatment with any of the prohibited concomitant medications: additional experimental anti-cancer treatment and/or standard chemotherapy, immunotherapy, hormone treatment or radiotherapy; P-gp inhibitors
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00748709


Locations
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United States, California
1200.26.3 Boehringer Ingelheim Investigational Site
Los Angeles, California, United States
United States, Colorado
1200.26.11 Boehringer Ingelheim Investigational Site
Denver, Colorado, United States
United States, Indiana
1200.26.9 Boehringer Ingelheim Investigational Site
Indianapolis, Indiana, United States
United States, Massachusetts
1200.26.1 Boehringer Ingelheim Investigational Site
Boston, Massachusetts, United States
United States, Nevada
1200.26.13 Boehringer Ingelheim Investigational Site
Las Vegas, Nevada, United States
United States, New York
1200.26.4 Boehringer Ingelheim Investigational Site
Albany, New York, United States
1200.26.2 Boehringer Ingelheim Investigational Site
New York, New York, United States
United States, Ohio
1200.26.7 Boehringer Ingelheim Investigational Site
Kettering, Ohio, United States
United States, Texas
1200.26.12 Boehringer Ingelheim Investigational Site
Dallas, Texas, United States
1200.26.8 Boehringer Ingelheim Investigational Site
Tyler, Texas, United States
United States, Virginia
1200.26.6 Boehringer Ingelheim Investigational Site
Norfolk, Virginia, United States
United States, Washington
1200.26.10 Boehringer Ingelheim Investigational Site
Vancouver, Washington, United States
Taiwan
1200.26.88603 Boehringer Ingelheim Investigational Site
Tainan, Taiwan
1200.26.88601 Boehringer Ingelheim Investigational Site
Taipei, Taiwan
1200.26.88602 Boehringer Ingelheim Investigational Site
Tao-Yuan, Taiwan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
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Study Chair: Boehringer Ingelheim Boehringer Ingelheim
More Information
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Additional Information:

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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00748709    
Other Study ID Numbers: 1200.26
First Posted: September 9, 2008    Key Record Dates
Results First Posted: October 14, 2013
Last Update Posted: November 28, 2013
Last Verified: November 2013
Additional relevant MeSH terms:
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Afatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action