The purpose of this trial is to determine if rash caused by erlotinib can be successfully treated and if so to determine the optimal treatment approach. Hypothesis: Hypothesis 1: If the incidence of rash is 50% while on erlotinib, prophylactic monotherapy with minocycline can prevent occurrence in 50% of these patients. Hypothesis 2: Treatment of rash is successful in improving rash by at least one Grade in 80% of patients. Hypothesis 3: In patients with untreated rash, the rash will be self-limiting in 25% of patients, and 65% will be grade 1, 2A, and 2b. Ten percent will be grade 3 requiring treatment with monotherapy intervention.
Erlotinib has been shown to prolong survival in NSCLC patients who are no longer candidates for further chemotherapy. In July 2005, erlotinib was approved in Canada for the treatment of patients with locally advanced or metastatic NSCLC, following failure of first or second-line chemotherapy. Erlotinib's side effect profile includes rash. The incidence of rash in clinical trials has been reported to be approximately 50 - 75%, and has been hypothesised to parallel tumour response (20). The treatment of rash is controversial and many oncologists believe it is untreatable and self-limiting. The cause of the rash is not well understood but is felt to be a systemic event. Clinical experience of the investigators has suggested that minocycline 100 mg orally given twice-daily for 4 weeks and clindamycin 2% and hydrocortisone 1% topical cream for moderate to severe rash is a successful treatment. The objectives of this trial are to better delineate the rash and its features and to describe an optimal treatment. Since the rash is often facial in distribution and can therefore lead to physical and psychological distress to the patient, a dermatology life quality index will also be completed throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
Patients will receive prophylactic treatment with minocycline 100 mg orally twice-daily for at least 4 weeks on the initiation of erlotinib therapy. If rash occurs during the 4 week period of minocycline prophylaxis, the minocycline prophylaxis will continue and additional treatment by grade of rash will be according to the Treatment Arm 2 schedule. If rash occurs after the completion of the 4 week prophylaxis period, treatment by grade of rash will be according to the Treatment Arm 2 schedule.
Appropriate amounts of clindamycin and hydrocortisone powder are mixed with corresponding amount of Nutraderm® lotion for this mixture. If preferred, the appropriate amount of clindamycin powder can be mixed with Emo-Cort® lotion (already contains hydrocortisone 1%), available in 60 mL bottles.
Erlotinib will be given on an outpatient basis at a fixed dose of either 150 or 100 mg as a single daily oral dose.
Clindamycin 2% in Triamcinolone acetonide 0.1% solution in equal parts propylene glycol and water
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
BC Cancer Agency - Abbotsford
Abbotsford British Columbia, British Columbia, Canada
Burnaby Hospital Regional Cancer Centre
Burnaby, British Columbia, Canada
BC Cancer Agency - Fraser Valley Centre
Vancouver, British Columbia, Canada
BC Cancer Agency Vancouver Centre
Vancouver, British Columbia, Canada
BC Cancer Agency - Vancouver Island Centre
Victoria, British Columbia, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
Princess Margaret Hospital
Toronto, Ontario, Canada
Overall Incidence of Rash
The overall incidence of any grade of erlotinib-induced rash among the three treatment arms. For overall incidence of rash a binary variable will be designed. Data will be summarized with percentages by treatment group.
Time frame: From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year
Time Duration From Onset of Rash Until Resolution
To investigate if the rash caused by erlotinib is self-limiting. A time variable will be defined to identify the duration from onset of rash until resolution. Resolution will be defined as resolution to severity Grade 1 for patients with rash of maximum severity grade \>1 and resolution to Grade 0 for patients with maximum rash severity = 1. For patients where resolution is not observed the time considered will be the maximum time from onset of rash until end of the study. The analyses will be performed using the following two sub-populations: subjects with maximum severity of rash of Grade 1, 2a and 2b will constitute one sub-population and Grade 3 will be considered the second sub-population. The comparisons will be performed primarily for Group 1 vs. Group 3 and Group 2 vs. Group 3 and secondly for Group 1 vs. Group 2.
Time frame: From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year
Overall Incidence of Grade 3 Rash
The overall incidence of grade 3 erlotinib-induced rash among the three treatment arms. For overall incidence of rash a binary variable will be designed. Data will be summarized with percentages by treatment group.
Time frame: From onset of rash until resolution, up to 4 weeks following progression, on average of 1 year
Severity of Rash Caused by Erlotinib
The maximum severity of rash per subject will be summarized by treatment group. The summary will include only subjects who indicated any occurrence of rash.
Time frame: Onset until resolution, up to 4 weeks following progression, on average of 1 year
Overall Survival
Time frame: Until death
Duration of Treatment
Time frame: Up to one year
Time to First Presentation of Rash
Time frame: Up to onset of rash while on study treatment
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