Treatment With BIBW 2992, Irreversible Inhibitor of EGFR and HER-2 in Non Small Cell Lung Cancer (NSCLC)
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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.
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 3,200 patients who progressed to cytotoxic chemotherapy and EGFR inhibitors, recruited from 300 centers in 30 different countries.
The propose of this study in patients from the National Cancer Institute, 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Non-Small Cell Lung Cancer EGFR Tyrosine Kinase Inhibitor 324674 |
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 |
- Response Rate or objective response [ 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 or target [ 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 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
| Estimated Enrollment: | 150 |
| Study Start Date: | August 2010 |
| Estimated Study Completion Date: | December 2012 |
| Estimated Primary Completion Date: | August 2012 (Final data collection date for primary outcome measure) |
-
Drug: BIBW 2992
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Oscar G Arrieta, MD M Sc | 56 28 04 00 ext 353 | ogar@unam.mx |
| Mexico | |
| National Cancer Institute of Mexico | Recruiting |
| Mexico city, Distrito Federal, Mexico, 14080 | |
| Principal Investigator: | Oscar G Arrieta, MD M Sc | Mexico. National Cancer Institute |
More Information
Additional Information:
Publications:
| Responsible Party: | Oscar Gerardo Arrieta Rodriguez MD, MD M Sc, 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: | February 24, 2012 |
| 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 May 23, 2013