Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non Small Cell Lung Cancer (NSCLC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Instituto Nacional de Cancerologia de Mexico
Sponsor:
Information provided by (Responsible Party):
Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier:
NCT01542437
First received: February 24, 2012
Last updated: June 29, 2013
Last verified: June 2013
  Purpose

Non Small Cell Lung Cancer (NSCLC) is a health problem that continues to have a poor prognosis. The positive impact of chemotherapy is limited by the developed of intrinsic and acquired resistance, manifested clinically by progression early and transient responses. Current chemotherapy regimens have limited efficacy, with a modest benefit in terms of survival and leads to significant toxicity resulting in many patients can not receive this treatment, even in the context of firstling therapy. Therefore, there is great need to provide patients with less toxic agents, including novel targeted therapies with the potential to improve efficacy and maintain good quality of life with low toxicity.

BIBW 2992, an irreversible inhibitor of receptor Epidermal growth factor type 1/2 (EGFR/HER2) has shown benefit as a single agent in pretreated patients who have progressed despite platinum-based chemotherapy with minimal toxicity. BIBW 2992 is also currently (EGFR), with promising preliminary results of efficacy. In a phase II arm used BIBW 2992 in patients with lung adenocarcinoma with EGFR mutations, shows evidence of a definitive clinical benefit provided by the irreversible EGFR inhibitor BIBW 2992 in patients with NSCLC.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Positive EGFR Mutation
Drug: BIBW 2992
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non Small Cell Lung Cancer in Advanced Stage, Which Have Progressed to Chemotherapy. Analysis of Mutations in EGFR, KRAS and Number of Copies of HER-2

Resource links provided by NLM:


Further study details as provided by Instituto Nacional de Cancerologia de Mexico:

Primary Outcome Measures:
  • Response Rate [ Time Frame: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died. ] [ Designated as safety issue: Yes ]
    Is assigned to each subject the best objective response according to the investigator's decision (according to RECIST criteria). This is defined as the best response recorded from the start of treatment until progression / recurrence of disease. For patients with response status partial (PR) or complete response (CR), changes in tumor measurements must be confirmed by repeated assessments to be made not less than 4 weeks after it first reached the response criteria The CT will be made every two months to assess response to treatment. The objective response will be summarized descriptively.

  • Global control [ Time Frame: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died. Response rate was measured every 4 weeks ] [ Designated as safety issue: Yes ]
    Is defined by the sum of partial responses, complete responses and stable disease, excluding only the rate of progression. These are measured by RECIST criteria.

  • Progression Free Survival [ Time Frame: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died. ] [ Designated as safety issue: Yes ]
    Is defined as the time from start of treatment until the date of the first documented evidence of progression (RECIST criteria) or the date of death for any reason in the absence of disease progression (EP). For patients who have died or progressed at the time of final analysis, use the date of last contact.

  • Global survival [ Time Frame: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died. ] [ Designated as safety issue: Yes ]
    Overall survival will be determined from the date of commencement of treatment to date of death, regardless of the cause of death. In patients who did not die at the time of final analysis will use the date of last contact.


Secondary Outcome Measures:
  • quantification HER-2 [ Time Frame: baseline ] [ Designated as safety issue: Yes ]
    Assessing the number of copies of the HER-2 gene by FISH

  • Identification of mutations in EGFR and KRAS [ Time Frame: baseline ] [ Designated as safety issue: Yes ]
    Tumor samples were fixed in formalin and embedded in paraffin, used for histologic diagnosis of patients will be obtained from the Departments of Pathology participating institutes.

  • descriptive analysis of safety. [ Time Frame: from the start of consumption until at least 6 months after stopping BIBW 2992 or when all patients have died. ] [ Designated as safety issue: Yes ]
    adverse effect from CTCAE


Estimated Enrollment: 150
Study Start Date: August 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBW 2992 Drug: BIBW 2992
All patients will receive: BIBW 2992 50mg every 24 hours orally, where a cycle corresponds to complete this treatment for 28 days; option 40mg/día dose reductions and 30mg/day, according to established criteria. Not be compared with any other drug.
Other Name: Afatinib

Detailed Description:

This protocol will be proposed as a Phase II controlled trial, integrating a group of Mexican collaborative research of lung cancer. Whit this protocol, we hope to offer the possibility of access to treatment with BIBW2992 to patients who could benefit from this treatment, during the regulatory review process and before the license is granted BIBW 2992 in Mexico.

In a study extended use that is currently recruiting (BIBW 2992) investigates the response rate and safety data BIBW 2992 in approximately 80 patients who progressed to cytotoxic chemotherapy and EGFR inhibitors, recruited from Instituto Nacional de Cancerología.

The propose of this study is analyze in Mexican patients the response rate and safety data and provide this treatment after failure of first line platinum-based chemotherapy or without treatment only as a second line EGFR inhibitor therapy and will report independently to the study of extended use, adding to prognostic analysis of K-Ras mutations and EGFR and number of copies of HER2 by FISH.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of lung cancer non-small cell (stage IIIB or IV) inoperable, locally advanced, recurrent or metastatic, histologically or cytologically documented.
  • The patient must present evidence of measurable disease.
  • 18 years of age or older.
  • ECOG performance status of 0-2
  • Life expectancy at least 12 weeks.
  • lung cancer patients with advanced non-small cell, stage IIIB / IV who have received at least one cycle of systemic chemotherapy standard platinum-based first-or second-line fault has been documented that treatment.
  • are admissible 3 or more prior chemotherapy regimens. Patients must have recovered from any toxic effects and should have passed at least 2 weeks after the last dose prior to registration (14 days for vinorelbine and other vinca alkaloids or gemcitabine). Patients in the opinion of the investigator are fully recovered from surgery for 4 weeks at least, can also be considered for the study. Patients must have recovered from any severe toxicity (CTC ≤ 1) caused by any previous therapy.
  • granulocyte count ≥ 1.5x 109 / L and platelet count> 100 × 109 / L.
  • serum bilirubin should be ≤ 1.5 X ULN
  • AST and / or ALT ≤ 2 ULN (or ≤ 5 x ULN when clearly attributable to the presence of liver metastases).
  • Serum creatinine ≤ 1.5 (ULN) or creatinine clearance ≥ 60ml/min
  • Ability to comply with study procedures and monitoring.
  • Of all women of childbearing potential should be obtained a negative pregnancy test within 72 hours before the start of therapy.
  • Patients with reproductive potential must use effective contraception.
  • Written informed consent (signed) to participate in the study.

Exclusion Criteria:

  • Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, liver disease, renal or metabolic).
  • Pre-treatment with systemic anti-tumor therapy with EGFR inhibitors (tyrosine kinase inhibitors).
  • Any other malignancy within the previous 5 years (except for carcinoma in situ of the cervix or skin cancer adequately treated basal cell type).
  • Excluded patients with brain metastases or spinal cord compression of newly diagnosed and / or have not been definitively treated with surgery and / or radiation, supporting both patients with CNS metastases or spinal cord compression previously diagnosed and treated with evidence of stable disease (clinically stable on imaging studies) for a minimum of 2 months.
  • Any significant ophthalmologic abnormality, especially severe syndrome of dry eye, keratoconjunctivitis sicca, Sjogren's syndrome, severe keratitis exposure and any other condition that may increase the risk of corneal epithelial damage. We do not recommend the use of contact lenses during the study. The decision to continue with the use of contact lenses should be discussed with the treating oncologist and the patient's ophthalmologist.
  • Patients unable to take oral medication, requiring intravenous nutrition, which have undergone prior surgical procedures affecting absorption, or who have active peptic ulceration.
  • lactating women.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01542437

Contacts
Contact: Oscar Arrieta, MD M Sc 56 28 04 00 ext 353 ogar@unam.mx

Locations
Mexico
National Cancer Institute of Mexico Recruiting
Mexico city, Distrito Federal, Mexico, 14080
Sponsors and Collaborators
Instituto Nacional de Cancerologia de Mexico
Investigators
Principal Investigator: Oscar Arrieta, MD M Sc Mexico. National Cancer Institute
  More Information

Additional Information:
Publications:

Responsible Party: Oscar Gerardo Arrieta Rodríguez MD, Principal Investigator, Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier: NCT01542437     History of Changes
Other Study ID Numbers: BIBW2992
Study First Received: February 24, 2012
Last Updated: June 29, 2013
Health Authority: Mexico: Ethics Committee

Keywords provided by Instituto Nacional de Cancerologia de Mexico:
Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 27, 2014