Official Title: “A Randomized Controlled Trial of Systemic and Topical Treatments for Rash Secondary to Erlotinib in Advanced Stage IIIB or IV Non-Small Cell Lung Cancer”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

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.

Intervention(s) in this Clinical Trial

• Drug: minocycline; Lotion (clindamycin 2% /hydrocortisone 1%)

Primary Measures

• Overall incidence of rash
  • Time Frame: 1 year
    

Secondary Measures

• To investigate if the rash caused by erlotinib is self-limiting
  • Time Frame: 1 year
    

Inclusion Criteria:

• 1. Histologically or cytological documented diagnosis of inoperable, locally advanced, recurrent or metastatic (stage IIIB or stage IV) non-small cell lung cancer.
• 2. Evidence of disease (measurable disease is not mandatory).
• 3. 18 years of age or older.
• 4. ECOG performance status of 0 – 3.
• 5. Written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

Exclusion Criteria:

• 1. A history of another cancer other than basal cell carcinoma or cervical cancer in situ within the past 3 years
• 2. Prior therapy with any type of cancer growth factor inhibitor (EGFR inhibitor or agent targeting this family of growth factor receptors)
• 3. Life expectancy of less than 12 weeks.
• 4. Ongoing toxic effects from prior chemotherapy.
• 5. Pregnant or lactating women.
• 6. Females of childbearing potential who have a positive or no pregnancy test (pregnancy tests must be obtained within 72 hours before starting therapy). (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).
• 7. Male or female patients with reproductive potential who are unwilling to use effective and reliable contraceptive methods throughout the course of the study and for 90 days after the last dose of study medication.
• 8. Ongoing treatment with any inhibitors or inducers of CYP3A4 activity
• 9. Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease).
• 10. Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions.
• 11. Unwilling or unable to comply with the protocol for the duration of the study.
• 12. Patients who have experienced prior hypersensitivity reaction to active ingredients or excipients of the following compounds: erlotinib, minocycline, tetracycline, doxycycline or clindamycin.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: British Columbia Cancer Agency

Overall Clinical Trial Officials and Contacts

Barb Melosky, MD Principal Investigator BC Cancer Agency  

Overall Contact: Barb Melosky, MD 604 877-6000 bmelosky@bccancer.bc.ca

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00473083

Study ID Number: ML21016

ClinicalTrials.gov Identifier: NCT00473083

Health Authority: Canada: Health Canada