Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non Small Cell Lung Cancer (NSCLC)
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.
Non-Small Cell Lung Cancer
Positive EGFR Mutation
Drug: BIBW 2992
|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|
- 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.
- 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
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|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/day dose reductions and 30mg/day, according to established criteria.
Not to be compared with any other drug.
Other Name: Afatinib
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01542437
|Contact: Oscar Arrieta, MD M Sc||56 28 04 00 ext email@example.com|
|National Cancer Institute of Mexico||Recruiting|
|Mexico city, Distrito Federal, Mexico, 14080|
|Principal Investigator:||Oscar Arrieta, MD M Sc||Mexico. National Cancer Institute|