Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Exanthema

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Anti-Infective Agents

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Doxycycline

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Doxycline

erlotinib [Tarceva]

Clinical Trials

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.

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

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

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.

A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustular and nodules.

A cutaneous rash as folliculitis can be defined with several types including erythema, papulo-pustule, nodule, and crust.

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.

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.

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 without skin rash (folliculitis) at 4 months.

Percentage of participants estimated to be without skin rash (folliculitis) at 12 months.

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.

If the end of cutaneous rash was missing, the duration of cutaneous rash was calculated between start of folliculitis and last evaluation date.

Other skin lesions included presence or absence of xerosis and paronychia.

Other skin lesions included xerosis and paronychia.

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.

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.

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.

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).

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.

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.

OS was defined by the time between first intake of treatment with erlotinib and death for any cause; analyzed using Kaplan-Meier method.

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.

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 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).

Hoffmann-La Roche

Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.

Erlotinib + Doxycycline

Participants received erlotinib 150 mg/day, tablets, PO until progression or unacceptable toxicity.

Erlotinib

Total

Age, Continuous

Sex: Female, Male

Intent-to-Treat population (ITT): all randomized participants who received at least

1 dose of erlotinib.

Medical Communications

ITT population; data for 1 participant in the erlotinib treatment group were missing.

Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade During the First 4 Months of Treatment

Number of Skin Rash (Folliculitis) Events During the First 4 Months of Treatment

Erythema

Papulo-pustule

Nodule

Crust

Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Type

Erlotinib + doxycycline vs Erlotinib: Grade 3 intensity skin rash (folliculitis)

Grade 1

Grade 2

Grade 3

ITT population; only participants with an adverse event of skin rash (folliculitis) during the first 4 months were included in the analysis.

Percentage of Participants With Skin Rash (Folliculitis) During the First 4 Months of Treatment By Maximal Intensity

Percentage of Participants With at Least One Skin Rash (Folliculitis) of Any Grade After the First 4 Months of Treatment

Number of Skin Rash (Folliculitis) Events After the First 4 Months of Treatment

Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Type

Initial intensity: Grade 1

Maximal intensity: Grade 1

Number of Participants With Skin Rash (Folliculitis) After the First 4 Months of Treatment By Intensity

Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Number of Participants With an Event

Time Free From Skin Rash (Folliculitis) During the First 4 Months of Treatment - Time to Event

Percentage of Participants Estimated to be Event Free at 4 Months

Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Number of Participants With an Event

Time Free From Skin Rash (Folliculitis) During the Whole Treatment Period - Time to Event

Percentage of Participants Estimated to be Event Free at 12 Months

ITT Population; only participants with an event (folliculitis) were included in the analysis.

Duration of Skin Rash (Folliculitis) During the First 4 Months of Treatment

Duration of Skin Rash (Folliculitis) During the Whole Treatment Period

Percentage of Participants With Other Skin Lesions of Any Grade During the First 4 Months of Treatment

Xerosis

Paronychia

Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Type

Erlotinib + doxycycline vs Erlotinib: Grade 3

Grade 4

ITT population; only participants with an adverse event classified as other skin lesion during the first 4 months were included in the analysis.

Percentage of Participants With Other Skin Lesions During the First 4 Months of Treatment By Maximal Intensity

Adverse event

Investigator's decision

Other

ITT population; only participants that discontinued or interrupted erlotinib were included in the analysis.

Percentage of Participants With Erlotinib Dose Reduction by Reason for Reduction

ITT population; only participants that discontinued or interrupted doxycycline were included in the analysis.

Percentage of Participants With Doxycycline Dose Reduction by Reason for Reduction

Month 2 (n=34,33)

Month 4 (n=19,25)

Month 7 (n=11,17)

Month 10 (n=7,12)

Month 12 (n=7,10)

ITT population; number (n) = number of participants analyzed for the specified parameter at a given visit.

Percentage of Participants With Global Disease Control by Visit

Progression

Percentage of Participants by Best Global Response Under Treatment

Progression-Free Survival (PFS) - Percentage of Participants With an Event

Progression-Free Survival (PFS) - Time to Event

4 Months

12 Months

Percentage of Participants Estimated to be Progression Free at 4 and 12 Months

Overall Survival (OS) - Percentage of Participants With an Event

Overall Survival (OS) - Time to Event

Percentage of Participants Estimated to be Alive at 4 and 12 Months

Baseline (n=67,69)

Day 14 (n=63,62)

Day 28 (n=60,56)

Month 2 (n=35,37)

Month 3 (n=29,27)

Month 4 (n=19,24)

Endpoint (n=65,63)

Change at Endpoint (n=35,37)

ITT Population; n=number of participants assessed for the specified parameter at a given visit.

Dermatology Life Quality Index (DLQI) Global Score

Baseline, no effect (n=67,69)

Baseline, small effect (n=67,69)

Day 14, no effect (n=63,62)

Day 14, small effect (n=63,62)

Day 14, moderate effect (n=63,62)

Day 14, very large effect (n=63,62)

Day 14, extremely large effect (n=63,62)

Day 28, no effect (n=60,56)

Day 28, small effect (n=60,56)

Day 28, moderate effect (n=60,56)

Day 28, very large effect (n=60,56)

Day 28, extremely large effect (n=60,56)

Month 2, no effect (n=35,37)

Month 2, small effect (n=35,37)

Month 2, moderate effect (n=35,37)

Month 2, very large effect (n=35,37)

Month 2, extremely large effect (n=35,37)

Month 3, no effect (n=29,27)

Month 3, small effect (n=29,27)

Month 3, moderate effect (n=29,27)

Month 3, very large effect (n=29,27)

Month 4, no effect (n=19,24)

Month 4, small effect (n=19,24)

Month 4, very large effect (n=19,24)

Percentage of Participants by DLQI Global Score Classification of Disease Effect on Quality of Life

Baseline (n=64,68)

Day 14 (n=62,63)

Change at Day 14 (n=59,61)

Day 28 (n=59,56)

Change at Day 28 (n=55,54)

Month 2 (n=36,36)

Month 3 (n=28,27)

Month 4 (n=18,24)

Endpoint (n=65,64)

Change at Endpoint (n=60,62)

ITT population; n=number of participants assessed for the specified parameter at a given visit.

Quality of Life Score as Assessed by Visual Analog Scale (VAS)

Participants received erlotinib 150 milligrams per day (mg/day), tablets, orally (PO) until progression or unacceptable toxicity and doxycycline 100 mg/day, tablets, PO for the first 4 months of the study; after this period it was the investigator's choice to continue treatment with doxycycline.

Spots Global Cancer Trial Database for A Study of Management of Tarceva - Induced Rash in Patients With Non-Small Cell Lung Cancer.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial