Systemic and Topical Treatments for Rash Secondary to Erlotinib in Lung Cancer (LUTRAERL)

February 16, 2017 updated by: British Columbia Cancer Agency

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

150

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Abbotsford, British Columbia, Canada, V2S 0C2
        • BC Cancer Agency - Abbotsford
      • Burnaby, British Columbia, Canada, V5G 2X6
        • Burnaby Hospital Regional Cancer Centre
      • Vancouver, British Columbia, Canada, V3V 1Z2
        • BC Cancer Agency - Fraser Valley Centre
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer Agency Vancouver Centre
      • Victoria, British Columbia, Canada, V8R 6V5
        • BC Cancer Agency - Vancouver Island Centre
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital
      • Toronto, Ontario, Canada, M5G 1Z6
        • Princess Margaret Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm 1: Prophylactic Treatment
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.
Drug: Minocycline
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.
Other Names:
  • Minocin
  • Dynacin
  • Minocin PAC
  • Myrac
  • Solodyn
  • Vectrin
Drug: Clindamycin 2% in hydrocortisone 1% lotion

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.

Drug: Erlotinib
Erlotinib will be given on an outpatient basis at a fixed dose of either 150 or 100 mg as a single daily oral dose.
Other Names:
  • Tarceva
Drug: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln
Clindamycin 2% in Triamcinolone acetonide 0.1% solution in equal parts propylene glycol and water
EXPERIMENTAL: Arm 2: Reactive Treatment

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.
Drug: Minocycline
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.
Other Names:
  • Minocin
  • Dynacin
  • Minocin PAC
  • Myrac
  • Solodyn
  • Vectrin
Drug: Clindamycin 2% in hydrocortisone 1% lotion

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.

Drug: Erlotinib
Erlotinib will be given on an outpatient basis at a fixed dose of either 150 or 100 mg as a single daily oral dose.
Other Names:
  • Tarceva
Drug: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln
Clindamycin 2% in Triamcinolone acetonide 0.1% solution in equal parts propylene glycol and water
EXPERIMENTAL: Arm 3: No Treatment Unless Severe (Grade 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.
Drug: Minocycline
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.
Other Names:
  • Minocin
  • Dynacin
  • Minocin PAC
  • Myrac
  • Solodyn
  • Vectrin
Drug: Clindamycin 2% in hydrocortisone 1% lotion

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.

Drug: Erlotinib
Erlotinib will be given on an outpatient basis at a fixed dose of either 150 or 100 mg as a single daily oral dose.
Other Names:
  • Tarceva
Drug: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln
Clindamycin 2% in Triamcinolone acetonide 0.1% solution in equal parts propylene glycol and water

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Incidence of Rash
Time Frame: From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year

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.
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
Time Frame: From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year

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.
From onset of rash until resolution, up to 4 weeks following progression, an average of 1 year
Overall Incidence of Grade 3 Rash
Time Frame: From onset of rash until resolution, up to 4 weeks following progression, on average of 1 year

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.
From onset of rash until resolution, up to 4 weeks following progression, on average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of Rash Caused by Erlotinib
Time Frame: Onset until resolution, up to 4 weeks following progression, on average of 1 year
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.
Onset until resolution, up to 4 weeks following progression, on average of 1 year
Overall Survival
Time Frame: Until death
Until death
Duration of Treatment
Time Frame: Up to one year
Up to one year
Time to First Presentation of Rash
Time Frame: Up to onset of rash while on study treatment
Up to onset of rash while on study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

British Columbia Cancer Agency

Collaborators

Hoffmann-La Roche

Investigators

  • Principal Investigator: Barb Melosky, MD, British Columbia Cancer Agency

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (ACTUAL)

December 1, 2012

Study Completion (ACTUAL)

August 1, 2013

Study Registration Dates

First Submitted

May 10, 2007

First Submitted That Met QC Criteria

May 10, 2007

First Posted (ESTIMATE)

May 14, 2007

Study Record Updates

Last Update Posted (ACTUAL)

April 4, 2017

Last Update Submitted That Met QC Criteria

February 16, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML21016

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Rash

Clinical Trials on Minocycline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe