Tetracycline as a Prophylaxis for Rash in Patients With NSCLC Receiving Treatment With BIBW2992 (Afatinib)
- Advanced NSCLC has a poor prognosis and the positive impact of chemotherapy is limited by the development of intrinsic and acquired resistance.
- Over the past decade, less toxic agents such as the innovative targeted therapies, i.e. erlotinib or gefitinib, have the potential to improve the effectiveness and keep a good quality of life with a low toxicity
- BIBW2992 (afatinib), an aniline-quinazoline, is an epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2) irreversible inhibitor, and it has activity against erlotinib-resistant isoforms having mutations in EGFR and HER-2.
- This molecule has shown benefits as a single agent in pre-treated patients who have progressed despite platinum-based chemotherapy, with a minimal toxicity compared to chemotherapy.
- BIBW2992 is associated with adverse effects similar to those for erlotinib and gefitinib, such as rash and diarrhea. These symptoms can reduce the quality of life (QL) in patients and lead to inconsistent EGFR inhibitor dose administration
- There is not a standard treatment for rash. However, case reports have tried to demonstrate the benefit in the treatment of these cutaneous injuries obtained with alcohol-free emollients, sunscreen with titanium dioxide or antibiotic (topic or oral) treatment regimens that include clindamycin or doxycycline, as well as anti-inflammatory drugs such as steroids and isotretinoin.
- In order to reduce the incidence and severity of cutaneous toxicities, we will compare the prophylactic antibiotic treatment using tetracycline and general dermatological recommendations versus using only dermatological recommendations, in patients initiating the treatment with BIBW2992.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
|Official Title:||Phase II, Open-label, Single Blind, Randomised Clinical Trial With Tetracycline as a Prophylaxis for Rash and Dermatological Recommendations Versus Dermatological Recommendations in Patients With NSCLC Receiving Treatment With BIBW 2992|
- Frequency of Participants Who Experienced Any Grade of Rash As Characterized By The Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0 [ Time Frame: Percentage of adverse events at week 8 ]Sum of participants who experienced any grade rash according to the Common Toxicity Criteria for Adverse Effects (CTCAE) V4.0, from the initiation of BIBW2992 compared to week 8.
- Quality of Life (QL) [ Time Frame: from baseline to 6 months ]A QL questionnaire from European Organization for Research and Treatment of Cancer (EORTC) organization (spanish version) will be performed at initiation of BIBW 2992 and then every month of follow-up until progression
- Progression Free-survival [ Time Frame: 24 weeks from baseline ]The measure will be from the start of consumption to the first documented evidence of progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, or if patients still survive the measure will be made after 24 weeks
- Progression Free Survival [ Time Frame: Participants will be followed for the duration of the treatment, an average of 8 weeks. ]From the start of consumption of BIBW 2992 to the date progression or last follow up
|Study Start Date:||December 2010|
|Study Completion Date:||November 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Patients will receive tetracycline 250mg every 12 hours for 1 month plus general dermatological recommendations (sunscreen and emollient cream)
The experimental group will receive tetracycline 250mg every 12 hours for 1 month the same day at initiation of BIBW2992 whereas the non-intervention group will recieve general dermatological recomendations while on treatment with BIBW2992.
No Intervention: No Tetracycline
This arm only with general dermatologic recommendations. Patients in this arm can receive tetracycline after week 4 of assessment only if rash grade 3-4 occur
Case reports have tried to demonstrate the benefit in the treatment of rash obtained with: alcohol-free emollients used 2-3 times daily, sunscreen with titanium dioxide or zinc oxide with a skin protection factor (SPF) greater than 15, topic or oral antibiotic regimens (such as clindamycin, metronidazole, tetracyclines) when there is secondary infection as well as steroidal anti-inflammatory drugs (betamethasone, triamcinolone) and isotretinoin.
The objective of this project is to evaluate whether the prophylactic treatment with tetracycline can reduce dermatological toxicities such as rash, induced by the EGFR and HER-2 tyrosine kinase inhibitor BIBW 2992 in patients with non-small cell lung cancer.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01880515
|Instituto Nacional de Cancerología|
|México, D.F., Mexico city, Mexico, 14080|
|Principal Investigator:||Oscar Arrieta, M.D., M.Sc.||Instituto Nacional de Cancerología|