A Study of Management of Tarceva - Induced Rash in Patients With Non-Small Cell Lung Cancer.
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Drug: Doxycline
- Registration Number
- NCT00531934
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This 2 arm study will evaluate the management of Tarceva-induced skin rash in patients with non-small cell lung cancer who have failed first-line chemotherapy for advanced disease. Eligible patients will be randomized to receive a)doxycycline 100mg po daily or b)no preventative treatment; all patients will receive Tarceva 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 individuals.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 147
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 erlotinib [Tarceva] - 1 erlotinib [Tarceva] - 1 Doxycline -
- Primary Outcome Measures
Name Time Method Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment Days 0, 14, 28 and Months 2, 3, and 4 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
Name Time Method Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, and 4 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 Months 7, 10, and 12 Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment Months 7, 10, and 12 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 Months 7, 10, and 12 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 Months 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 Percentage of participants estimated to be without skin rash (folliculitis) at 12 months.
Duration of Skin Rash (Folliculitis) During the Whole Treatment Period Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, and 4 Other skin lesions included xerosis and paronychia.
Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity Days 0, 14, 28 and Months 2, 3, and 4 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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.
Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment Days 0, 14, 28 and Months 2, 3, and 4 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.
Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Months 2, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Months 4 and 12 Overall Survival (OS) - Percentage of Participants With an Event Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Days 0, 14, 28 and Months 2, 3, 4, 7, 10, and 12 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 Months 4 and 12 Dermatology Life Quality Index (DLQI) Global Score Baseline, Days 14 and 28 and Months 2, 3, and 4 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 Baseline, Days 14 and 28 and Months 2, 3, and 4 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) Baseline, Days 14 and 28, and Months 2, 3, and 4 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).