Clinical trial NCT00473083
Conditions: Rash
Keywords: Rash Erlotinib Lung Cancer
Sponsor: British Columbia Cancer Agency
Start date: 2009-01-01; Completion date: 2013-08-01
Enrollment: 150 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Participants 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. arm 2: Pts will receive treatment at initiation of rash. Tx is dependent on grading of rash as follows:

Grade 1 or 2A: Topical clindamycin 2%, with hydrocortisone 1% in lotion base applied twice daily until resolution of rash by one grade

Grade 2B: Topical clindamycin 2%, with hydrocortisone 1% in lotion base applied 2x daily and oral minocycline 100mg 2x daily for a min. of 4 weeks and continuing thereafter, as required, until resolution of rash by 1 grade. Scalp lesions will be treated with a topical clindamycin 2%, triamcinolone acetonide 0.1% soln.

Grade 3: Pts will discontinue tx with erlotinib 150mg for 1 week and restart at 100mg once daily.

Tx with topical clindamycin 2%, with hydrocortisone 1% in lotion base applied 2x daily and oral minocycline 100mg 2x daily for a min. of 4 weeks and continuing thereafter, as required, until resolution of rash to Grade 1 or 2A. Scalp lesions will be treated with a topical clindamycin 2%, triamcinolone acetonide 0.1% soln. arm 3: This is the control group. Patients will be treated only if grade 3 rash develops. For grade 3 rash, treatment will be in accordance with that of Grade 3 rash in Treatment Arm 2.
Interventions: intervention 1: Minocycline intervention 2: Clindamycin 2% in hydrocortisone 1% lotion intervention 3: Erlotinib intervention 4: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: Erlotinib will be given on an outpatient basis at a fixed dose of either 150 or 100 mg as a single daily oral dose. intervention 4: Clindamycin 2% in Triamcinolone acetonide 0.1% solution in equal parts propylene glycol and water

Protocol documents: