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

NCT00473083 | Completed Phase 2 Results

• 1 other identifier: ML21016
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 9

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.

Conditions

Rash

Keywords

Rash; Erlotinib; Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Overall Incidence of Rash

  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

  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

  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 Outcomes (4)

• Severity of Rash Caused by Erlotinib

  Onset until resolution, up to 4 weeks following progression, on average of 1 year

• Overall Survival

  Until death

• Duration of Treatment

  Up to one year

• Time to First Presentation of Rash

  Up to onset of rash while on study treatment

Study Arms (3)

Arm 1: Prophylactic Treatment

EXPERIMENTAL

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; Drug: Clindamycin 2% in hydrocortisone 1% lotion; Drug: Erlotinib; Drug: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln

Arm 2: Reactive Treatment

EXPERIMENTAL

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; Drug: Clindamycin 2% in hydrocortisone 1% lotion; Drug: Erlotinib; Drug: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln

Arm 3: No Treatment Unless Severe (Grade 3)

EXPERIMENTAL

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; Drug: Clindamycin 2% in hydrocortisone 1% lotion; Drug: Erlotinib; Drug: Topical clindamycin 2%, triamcinolone acetonide 0.1% soln

Interventions

Minocycline DRUG

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.

Also known as: Dynacin, Minocin, Minocin PAC, Solodyn, Vectrin, Myrac

Arm 1: Prophylactic Treatment; Arm 2: Reactive Treatment; Arm 3: No Treatment Unless Severe (Grade 3)

Clindamycin 2% in hydrocortisone 1% lotion DRUG

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.

Arm 1: Prophylactic Treatment; Arm 2: Reactive Treatment; Arm 3: No Treatment Unless Severe (Grade 3)

Erlotinib DRUG

Erlotinib will be given on an outpatient basis at a fixed dose of either 150 or 100 mg as a single daily oral dose.

Also known as: Tarceva

Arm 1: Prophylactic Treatment; Arm 2: Reactive Treatment; Arm 3: No Treatment Unless Severe (Grade 3)

Topical clindamycin 2%, triamcinolone acetonide 0.1% soln DRUG

Clindamycin 2% in Triamcinolone acetonide 0.1% solution in equal parts propylene glycol and water

Arm 1: Prophylactic Treatment; Arm 2: Reactive Treatment; Arm 3: No Treatment Unless Severe (Grade 3)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• British Columbia Cancer Agency: lead
• Hoffmann-La Roche: collaborator

Study Sites (9)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer Agency - Abbotsford

Abbotsford, British Columbia, V2S 0C2, Canada

Location

Burnaby Hospital Regional Cancer Centre

Burnaby, British Columbia, V5G 2X6, Canada

Location

BC Cancer Agency - Fraser Valley Centre

Vancouver, British Columbia, V3V 1Z2, Canada

Location

BC Cancer Agency Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BC Cancer Agency - Vancouver Island Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 1Z6, Canada

Location

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MeSH Terms

Conditions

Exanthema; Lung Neoplasms

Interventions

Minocycline; Clindamycin; Hydrocortisone; Erlotinib Hydrochloride; Triamcinolone Acetonide

Condition Hierarchy (Ancestors)

Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Triamcinolone; Pregnadienes; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Barbara Melosky, Principal Investigator
• Organization: BC Cancer Agency

BMelosky@bccancer.bc.ca

604-877-6000

Study Officials

• Barb Melosky, MD

  British Columbia Cancer Agency

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2007
• First Posted: May 14, 2007
• Study Start: January 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: August 1, 2013
• Last Updated: April 4, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-02

Locations

CA (9)