Clinical trial NCT00473083: Systemic and Topical Treatments for Rash Secondary to Erlotinib in Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rash
Keywords: Rash
Erlotinib
Lung Cancer
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2007-05-14
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Incidence of Rash
timeFrame: From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year
measure: Time Duration From Onset of Rash Until Resolution
timeFrame: From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year
measure: Overall Incidence of Grade 3 Rash
timeFrame: From onset of rash until resolution, up to 4 weeks following progression, on average of 1 year
Secondary outcomes:
measure: Severity of Rash Caused by Erlotinib
timeFrame: Onset until resolution, up to 4 weeks following progression, on average of 1 year
measure: Overall Survival
timeFrame: Until death
measure: Duration of Treatment
timeFrame: Up to one year
measure: Time to First Presentation of Rash
timeFrame: Up to onset of rash while on study treatment
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Abbotsford
country: Canada
facility: BC Cancer Agency - Abbotsford
state: British Columbia
city: Burnaby
country: Canada
facility: Burnaby Hospital Regional Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Agency - Fraser Valley Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Agency Vancouver Centre
state: British Columbia
city: Victoria
country: Canada
facility: BC Cancer Agency - Vancouver Island Centre
state: British Columbia
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: British Columbia Cancer Agency
name: Barb Melosky, MD
role: PRINCIPAL_INVESTIGATOR
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