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Tetracycline as a Prophylaxis for Rash in Patients With NSCLC Receiving Treatment With BIBW2992 (Afatinib)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier:
NCT01880515
First received: May 31, 2013
Last updated: March 1, 2017
Last verified: March 2017
  Purpose
  1. Advanced NSCLC has a poor prognosis and the positive impact of chemotherapy is limited by the development of intrinsic and acquired resistance.
  2. 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
  3. 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.
  4. 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.
  5. 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
  6. 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.
  7. 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.

Condition Intervention Phase
Skin Rash
Lung Cancer
Drug: Tetracycline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Enrollment: 107
Study Start Date: December 2010
Study Completion Date: November 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tetracycline
Patients will receive tetracycline 250mg every 12 hours for 1 month plus general dermatological recommendations (sunscreen and emollient cream)
Drug: Tetracycline
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.
Other Names:
  • Tetracycline hydrocloride
  • Tetrex®
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

Detailed Description:

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.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of non-operable, locally advanced, recurrent or metastatic, histologically or cytologically documented non-small cell lung cancer (stage IIIB or IV).

    • Patients should have an evidence of measurable disease.
    • 18 years or older
    • Eastern Cooperative Oncology Group - Performance Status 0-3
    • At least 12 weeks of life expectancy
    • Patients with non-small cell lung cancer stages IIIB/IV who have received at least one cycle of platinum-based, first or second line systemic standard chemotherapy, and have a documented failure for this treatment.
    • More than 2 previous chemotherapy regimens are not allowed. The patients should have recovered from any toxic effect and at least 2 weeks should have elapsed from last dose before their entry (14 days for vinorelbine and other vinca alkaloids or gemcitabine). Patients who in the investigator's opinion are fully recovered from surgery for at least 4 weeks may also be considered for the study. Patients should have recovered from any severe toxicity (CTC > 1) caused by any previous therapy.
    • Granulocyte count > 1.5x 109/L and platelet count > 100x 109/L.
    • Serum bilirubin > 1.5 upper limit of normal (ULN)
    • AST and/or ALT > 2 ULN (or >5 x ULN when clearly attributable to presence of hepatic metastases).
    • Serum creatinine > 1.5 ULN or creatinine clearance < 60 mL/min
    • Capability to fulfill the study and follow-up procedures.
    • A negative pregnancy test should be obtained from all women of childbearing potential within 72 hours previous to therapy beginning.
    • Patients of reproductive potential should use effective contraceptive methods.
    • Written (signed) informed consent to participate in the study

Exclusion Criteria:

  • Patients allergic to the antibiotic therapy used.
  • Any unsteady systemic disease (including active infection, uncontrolled hypertension, unsteady angina, congestive cardiac failure, hepatic, renal or metabolic disease).
  • A previous treatment using a systemic anti-tumor therapy with EGFR inhibitors (tyrosine kinase inhibitors).
  • Any other malignant pathology within 5 previous years (except for carcinoma in situ of cervix or basal-cell type skin cancer appropriately treated).
  • Patients with cerebral metastases or spinal marrow compression recently diagnosed and/or definitely surgery and/or radiation naïve-treatment patients are excluded. Those with previously diagnosed and treated metastasis to Central Nervous System (CNS) or spinal marrow compression, having an evidence of steady disease (clinically steady in imaging studies) are accepted for at least 2 months.
  • Any significant ophthalmologic abnormality, especially severe dry-eye syndrome, keratoconjunctivitis sicca, Sjögren's syndrome, severe exposure keratitis and any other disorder that may increase the risk for corneal epithelial injure. Contact lens use during the study is not recommended. The decision to continue to use contact lens should be discussed with the oncologist responsible for patient treatment and the ophthalmologist.
  • Patients who cannot take oral medication, requiring intravenous nutrition, who underwent previous surgical procedures affecting absorption, or with active peptic ulcer.
  • Nursing 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: NCT01880515

Locations
Mexico
Instituto Nacional de Cancerología
México, D.F., Mexico city, Mexico, 14080
Sponsors and Collaborators
Instituto Nacional de Cancerologia de Mexico
Investigators
Principal Investigator: Oscar Arrieta, M.D., M.Sc. Instituto Nacional de Cancerología
  More Information

Publications:
C. Yang, J. Shih, W. Su, Et.Al. A phase II study of BIBW 2992 in patients with adenocarcinoma of the lung and activating EGFR mutations (LUX-Lung 2).- J Clin Oncol 28: 15s, 2010 (Suppl; Abstr 7521).
C. Yang, J. Shih, T. Chao, C. Tsai, Et.Al. Use of BIBW 2992, a novel irreversible EGFR/HER2 TKI, to induce regression in patients with adenocarcinoma of the lung and activating EGFR mutations: Preliminary results of a single-arm phase II clinical trial. J Clin Oncol 26: 2008
Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec, Brennscheidt U, De Rosa F, Mueller B, Von Pawel J: Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine (GC) chemotherapy in advanced non-small cell lung cancer (NSCLC) ASCO Annual Meeting 2004 abstract number 7010
Collen G., Vos L.E., Laurijsen A., Clasificación y tratamiento de los efectos secundarios de los inhibidorres del receptor de factor de crecimiento epidérmico (EGFR) en piel, pelo, uñas y mucosas. European Journal of Cancer. 2007, Vol 43: 845-851

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Oscar Gerardo Arrieta Rodríguez MD, M.D., M.Sc., Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier: NCT01880515     History of Changes
Other Study ID Numbers: TEPR-BIBW2992
Study First Received: May 31, 2013
Results First Received: June 17, 2015
Last Updated: March 1, 2017

Keywords provided by Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico:
Lung cancer
BIBW 2992
Skin Rash
Tetracycline
Afatinib

Additional relevant MeSH terms:
Exanthema
Skin Diseases
Tetracycline
Dermatologic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 25, 2017