Systemic and Topical Treatments for Rash Secondary to Erlotinib in Lung Cancer - Full Text View

Sponsor:	British Columbia Cancer Agency
Collaborator:	Hoffmann-La Roche
Information provided by:	British Columbia Cancer Agency
ClinicalTrials.gov Identifier:	NCT00473083

Purpose

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.

Condition	Intervention	Phase
Rash	Drug: minocycline; Lotion (clindamycin 2% /hydrocortisone 1%) Drug: minocycline Drug: clindamycin 2% and hydrocortisone 1%,	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Rashes

Drug Information available for: Hydrocortisone acetate Hydrocortisone Triamcinolone diacetate Triamcinolone acetonide Triamcinolone Hydrocortisone Sodium Succinate Hydrocortisone cypionate Triamcinolone hexacetonide Minocycline Minocycline hydrochloride Clindamycin hydrochloride Clindamycin phosphate Clindamycin Palmitate Hydrochloride Clindamycin palmitate Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by British Columbia Cancer Agency:

Primary Outcome Measures:

Overall incidence of rash [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To investigate if the rash caused by erlotinib is self-limiting [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	150
Study Start Date:	January 2009

Arms	Assigned Interventions
Experimental: Arm 1 Subjects (approximately 50) will be given minocycline (an antibiotic pill) 100mg orally to take for 4 weeks at the same time as starting their erlotinib to see if the rash can be prevented	Drug: minocycline Arm 1: Subjects (approximately 50) will be given minocycline (an antibiotic pill) 100mg orally to take for 4 weeks at the same time as starting their erlotinib to see if the rash can be prevented. If rash occurs then subjects will be treated using a medicated lotion, (clindamycin 2% and hydrocortisone 1%,) to be applied to the rash and if the rash is more severe, minocycline may be continued for more than 4 weeks.
Experimental: ARM 2 Arm 2: Subjects (Approximately 50) will be treated for the rash caused by erlotinib when it develops and the treatment will be a medicated lotion, (clindamycin 2% and hydrocortisone 1%,), applied to the rash and if the rash is more severe, minocycline 100mg orally twice daily. Scalp lesions will be treated with a topical clindamycin 2 %, triamcinolone acetonide 0.1% solution.	Drug: minocycline; Lotion (clindamycin 2% /hydrocortisone 1%) Subjects (Approximately 50) will be treated for the rash caused by erlotinib when it develops and the treatment will be a medicated lotion, (clindamycin 2% and hydrocortisone 1%,), applied to the rash and if the rash is more severe, minocycline 100mg orally twice daily. Scalp lesions will be treated with a topical clindamycin 2 %, triamcinolone acetonide 0.1% solution
Experimental: ARM 3 Arm 3: Subjects (Approximately 50) that develop the rash caused by erlotinib will only be treated if their rash becomes severe to see if it will go away itself. The treatment for severe rash will be medicated lotion, (clindamycin 2% and hydrocortisone 1%,), applied to the rash and minocycline 100mg orally twice daily. Scalp lesions will be treated with a topical clindamycin 2 %, triamcinolone acetonide 0.1% solution	Drug: clindamycin 2% and hydrocortisone 1%, Arm 3: Subjects (Approximately 50) that develop the rash caused by erlotinib will only be treated if their rash becomes severe to see if it will go away itself. The treatment for severe rash will be medicated lotion, (clindamycin 2% and hydrocortisone 1%,), applied to the rash and minocycline 100mg orally twice daily. Scalp lesions will be treated with a topical clindamycin 2 %, triamcinolone acetonide 0.1% solution.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically or cytological documented diagnosis of inoperable, locally advanced, recurrent or metastatic (stage IIIB or stage IV) non-small cell lung cancer.
Evidence of disease (measurable disease is not mandatory).
18 years of age or older.
ECOG performance status of 0 - 3.
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:

A history of another cancer other than basal cell carcinoma or cervical cancer in situ within the past 3 years
Prior therapy with any type of cancer growth factor inhibitor (EGFR inhibitor or agent targeting this family of growth factor receptors)
Life expectancy of less than 12 weeks.
Ongoing toxic effects from prior chemotherapy.
Pregnant or lactating women.
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).
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.
Ongoing treatment with any inhibitors or inducers of CYP3A4 activity
Any unstable systemic disease (including active infection, grade 4 hypertension, unstable angina, congestive heart failure, hepatic, renal or metabolic disease).
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.
Unwilling or unable to comply with the protocol for the duration of the study.
Patients who have experienced prior hypersensitivity reaction to active ingredients or excipients of the following compounds: erlotinib, minocycline, tetracycline, doxycycline or clindamycin.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00473083

Contacts

Contact: Barb Melosky, MD

604 877-6000 ext 2742

bmelosky@bccancer.bc.ca

Locations

Canada, British Columbia
BC Cancer Agency - Fraser Valley Centre	Recruiting
Vancouver, British Columbia, Canada, V3V 1Z2
Principal Investigator: Kevin Jasas, MD
BC Cancer Agency Vancouver Centre	Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Barb Melosky, MD 604-877-6000 ext 2017 bmelosky@bccancer.bc.ca
Principal Investigator: Barb Melosky, MD
Sub-Investigator: Janessa Laskin, MD
Sub-Investigator: Nevin Murray, MD
Sub-Investigator: Cheryl Ho, MD
BC Cancer Agency - Vancouver Island Centre	Not yet recruiting
Victoria, British Columbia, Canada, V8R 6V5
Principal Investigator: Anderson Helen, MD

Sponsors and Collaborators

British Columbia Cancer Agency

Hoffmann-La Roche

Investigators

Principal Investigator:

Barb Melosky, MD

British Columbia Cancer Agency

More Information

No publications provided

Responsible Party:	Dr Barb Melosky, British Columbia Cancer Agency
ClinicalTrials.gov Identifier:	NCT00473083 History of Changes
Other Study ID Numbers:	ML21016
Study First Received:	May 10, 2007
Last Updated:	November 3, 2010
Health Authority:	Canada: Health Canada

Keywords provided by British Columbia Cancer Agency:

Rash
Erlotinib
Lung Cancer

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Exanthema
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Skin Diseases
Clindamycin
Clindamycin-2-phosphate
Minocycline

Triamcinolone diacetate
Erlotinib
Cortisol succinate
Hydrocortisone acetate
Triamcinolone hexacetonide
Hydrocortisone
Triamcinolone Acetonide
Triamcinolone
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 22, 2012