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A Study of Management of Tarceva - Induced Rash in Patients With Non-Small Cell Lung Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00531934
First received: September 18, 2007
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

This 2 arm study will evaluate the management of Tarceva-induced skin rash in pa tients with non-small cell lung cancer who have failed first-line chemotherapy f or advanced disease. Eligible patients will be randomized to receive a)doxycycli ne 100mg po daily or b)no preventative treatment; all patients will receive Tarc eva 150mg/kg po daily. The anticipated time on study treatment is until disease progression or intolerable toxicity, and the target sample size is 100-500 indiv iduals.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Doxycline
Drug: erlotinib [Tarceva]
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open Label Study to Evaluate the Effect of Doxycycline on Tarceva-induced Skin Rash in Patients With Non-small Cell Lung Cancer After Failure of First Line Chemotherapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: Yes ]
    Description of skin rash (folliculitis, including erythema, papulo-pustules, nodule, and crust) was according to Common Terminology Criteria for Adverse Events (CTCAE) version 3 scale. Medical pictures of the face (front and sides views) systematically, and of any region presenting with skin lesions were obtained. The pictures were reviewed by a centralized committee of evaluation.


Secondary Outcome Measures:
  • Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.

  • Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.

  • Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Intensity of skin rashes was classified according to CTCAE grading. Grade 1 equals (=) Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering less than (<)50 percent (%) of body surface area (BSA); Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation.

  • Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment [ Time Frame: Months 7, 10, and 12 ] [ Designated as safety issue: No ]
  • Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment [ Time Frame: Months 7, 10, and 12 ] [ Designated as safety issue: No ]
    A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.

  • Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type [ Time Frame: Months 7, 10, and 12 ] [ Designated as safety issue: No ]
    A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.

  • Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity [ Time Frame: Months 7, 10, and 12 ] [ Designated as safety issue: No ]
    Intensity of skin rashes was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering <50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation.

  • Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.

  • Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.

  • Percentage of Participants Estimated to be Event Free at 4 Months [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Percentage of participants estimated to be without skin rash (folliculitis) at 4 months.

  • Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.

  • Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Period without occurrence was determined as the number of days from the first dose of medication until the first appearance of folliculitis, analyzed using Kaplan-Meier analysis.

  • Percentage of Participants Estimated to be Event Free at 12 Months [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Percentage of participants estimated to be without skin rash (folliculitis) at 12 months.

  • Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    If the cutaneous rash was ongoing at the last visit or Month 4, the duration of cutaneous rash was calculated between start of folliculitis and Visit Month 4 or premature withdrawal visit or death.

  • Duration of Skin Rash (Folliculitis) During the Whole Treatment Period [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    If the end of cutaneous rash was missing, the duration of cutaneous rash was calculated between start of folliculitis and last evaluation date.

  • Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Other skin lesions included presence or absence of xerosis and paronychia.

  • Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Other skin lesions included xerosis and paronychia.

  • Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity [ Time Frame: Days 0, 14, 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Other skin lesions included xerosis and paronychia. Intensity was classified according to CTCAE grading. Grade 1=Macular or papular eruption or erythema without associated symptoms; Grade 2=Macular or papular eruption or erythema with pruritus or other associated symptoms; localized desquamation or other lesions covering <50% of BSA; Grade 3=Severe, generalized erythroderma or macular, papular, or vesicular eruption; desquamation; Grade 4=Generalized exfoliative, ulcerative, or bullous dermatitis. If a participant had several skin lesions, the maximal intensity was taken into account.

  • Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Erlotinib dose adjustment was done in case of toxicity occurrence. Keratitis, diarrhea, interstitial lung disease, and other toxic occurrences determined erlotinib dose reduction. If erlotinib was previously discontinued for skin rash or diarrhea of Grade 2 and if these symptoms of Grade 2 recurred OR if the symptoms were intolerable for the participants, erlotinib was discontinued until recovery/Grade 1 then the dose was reduced of one level of 50 mg.

  • Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Occurrence of folliculitis-type skin rash of Grade greater than or equal to (≥)2 led to dose modification. Continuation of treatment with doxycycline after occurrence of folliculitis-type skin rash of Grade ≥2 was upon the investigator's opinion.

  • Percentage of Participants With Global Disease Control by Visit [ Time Frame: Months 2, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Disease control was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria for evaluation and was defined as participants with either complete response (CR), partial response (PR), or stable disease (SD).

  • Percentage of Participants by Best Global Response Under Treatment [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    Response was determined according to the RECIST criteria for evaluation and was defined as participants with either CR, PR, SD, or progression. No CR was reported.

  • Progression-Free Survival (PFS) - Percentage of Participants With an Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method.

  • Progression-Free Survival (PFS) - Time to Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    PFS was defined by the time between first intake of treatment with erlotinib and disease progression or death for any cause; estimated using Kaplan-Meier method.

  • Percentage of Participants Estimated to be Progression Free at 4 and 12 Months [ Time Frame: Months 4 and 12 ] [ Designated as safety issue: No ]
  • Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.

  • Overall Survival (OS) - Time to Event [ Time Frame: Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 ] [ Designated as safety issue: No ]
    OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.

  • Percentage of Participants Estimated to be Alive at 4 and 12 Months [ Time Frame: Months 4 and 12 ] [ Designated as safety issue: No ]
  • Dermatology Life Quality Index (DLQI) Global Score [ Time Frame: Baseline, Days 14 and 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. Analysis was performed by visit well as at the last available value after baseline (Endpoint); change from baseline to endpoint was also determined.

  • Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life [ Time Frame: Baseline, Days 14 and 28 and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Quality of life was assessed by participant's responses to a DLQI questionnaire. The DLQI is a 10-item questionnaire assessing quality of life; questions were assessed on a 4-point scale (0=not at all; 1=a little; 2=a lot; and 3=very much). The DLQI was calculated by summing the score of each question resulting in a maximum of 30 (extremely large effect on participant's life) and a minimum of 0 (no effect at all on participant's life). The higher the score, the more quality of life is impaired. The DLQI global score was classified into 5 levels: 0-1 (no effect at all), 2-5 (small effect), 6-10 (moderate effect), 11-20 (very large effect) and 21-30 (extremely large effect).

  • Quality of Life Score as Assessed by Visual Analog Scale (VAS) [ Time Frame: Baseline, Days 14 and 28, and Months 2, 3, and 4 ] [ Designated as safety issue: No ]
    Quality of life was assessed by participant's responses to a VAS questionnaire - (evaluation of satisfaction with skin status). VAS was measured on a 100 millimeter (mm) scale where 0 = not at all satisfied and 100 = very satisfied. Participants were asked to mark the line corresponding to their satisfaction at each visit and the distance from the left edge was measured. A negative change from baseline indicates improvement. Analysis was performed by visit well as at the last available value after baseline (Endpoint).


Enrollment: 147
Study Start Date: October 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Doxycline
100mg po daily
Drug: erlotinib [Tarceva]
150mg po daily
Active Comparator: 2 Drug: erlotinib [Tarceva]
150mg po daily

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, 18-75 years of age;
  • confirmed non-small cell lung cancer;
  • failure after first line chemotherapy for advanced disease, and scheduled for second line therapy with Tarceva.

Exclusion Criteria:

  • rash of any etiology at study entry;
  • history of significant heart disease;
  • any other malignancies (other than adequately treated squamous cell skin cancer, or in situ cancer of the cervix);
  • history of allergic reactions to tetracyclines.
  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: NCT00531934

Locations
France
Antibes, France, 06600
Bordeaux, France, 33076
Bordeaux, France, 33300
Brest, France, 29200
Caen, France, 14076
Chalon Sur Saone, France, 71100
Chartres, France, 28018
Draguignan, France, 83007
GAP, France, 05007
Gleize, France, 69400
Limoges, France, 87042
Metz, France, 57038
Nimes, France, 30900
Paris, France, 75116
Paris, France, 75674
Paris, France, 75679
Perigueux, France, 24000
Perpignan, France, 66000
Pierre Benite, France, 69495
Pontoise, France, 95300
Rennes, France, 35033
Rouen, France, 76000
Tours, France, 37044
Vannes, France, 56017
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00531934     History of Changes
Other Study ID Numbers: ML20829
Study First Received: September 18, 2007
Results First Received: June 23, 2014
Last Updated: November 3, 2014
Health Authority: France: Agence francaise de securite sanitaire des produits de sante (AFSSAPS)

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Erlotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on November 27, 2014