Official Title: “Evaluation of Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-Induced Rash”

A side effect occurring in a majority of patients taking erlotinib (Tarceva®) consists of a skin rash. Sometimes, symptoms associated with the rash necessitate erlotinib dose reduction or discontinuation. Some physicians have successfully treated the erlotinib-induced rash with doxycycline. At the same time, it has been observed that in patients who develop the erlotinib rash, the cancers respond better to erlotinib treatment. This research study is designed to determine how well doxycycline treats the erlotinib rash and whether doxycycline affects the blood levels of erlotinib.

Study Type: Interventional

Study Design: Supportive Care, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study

Study Primary Completion Date: October 2009

Intervention(s) in this Clinical Trial

• Drug: doxycycline
  • Doxycycline (the study drug) will be provided to all subjects as 100 mg tablets. They will be allocated enough doxycycline to last them until their next scheduled visit. The doxycycline tablets should be taken orally (only) at a dosage of 100 mg every 12 hours. Administration of adequate amounts of fluid along with capsule and tablet forms of drugs in the tetracycline class is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. The doxycycline tablets should not be taken with foods that contain calcium. The absorption of doxycycline is reduced when taking bismuth subsalicylate. Duration of study period if 14 days

Primary Measures

• The primary objective of this study is to determine whether administration of doxycycline affects erlotinib PK
  • Time Frame: 14 days
    Safety Issue?: No

Secondary Measures

• Secondarily, this study aims to investigate the relationship between erlotinib AUC and rash severity and to evaluate the efficacy of doxycycline in rash management.
  • Time Frame: 14 days
    Safety Issue?: No

Inclusion Criteria:

• Males and females 18 years of age or older.
• Subjects must have started Tarceva® therapy within three (3) days of trial enrollment.
• Patients must have signed informed consent prior to registration on study.
• Currently receiving erlotinib therapy at 150 mg per day for locally advanced or metastatic NSCLC.
• Patients - both males and females - with reproductive potential (ie, menopausal for less than 1 year and not surgically sterilized) must utilize barrier methods in combination with spermicidal agents for contraception when engaging in sexual intercourse. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.

Exclusion Criteria:

• Allergy to tetracyclines.
• Use of concurrent agents for papulopustular rash.
• Currently receiving anticancer agents other than erlotinib.
• Inability to interrupt other antibiotic therapy.
• Current use of topical steroids
• Current use of systemic immunosuppressants (e.g., methotrexate, cyclosporine, azathioprine, mycophenolate mofetil)
• Photosensitivity or lupus erythematosus.
• Active gastroesophageal reflux disease.
• Women who have a positive pregnancy test or are lactating by history.
• ECOG performance status ≤3.
• Self report of current smoking or history of smoking within 60 days of screening, or positive urine cotinine test.
• Current use of agents that are known to be strong inducers or inhibitors of CYTP3A4:
• inhibitors: atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi navir, ritonavir, saquinavir, telithromycin, troleandomycin (TAO), voriconazole, grapefruit or grapefruit juice
• inducers: rifampicin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, and St. John's Wort
• Impaired hepatic function (≤ 30 days before randomization):
• Alkaline phosphatase > 3x ULN
• Aspartate aminotransferase (AST) > x ULN
• Alanine aminotransferase (ALT) > 3 x ULN
• Total Bilirubin > 1.5 x ULN

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: Northwestern University

Overall Clinical Trial Officials and Contacts

Mario Lacouture, MD Principal Investigator Northwestern University  

Overall Contact: Mona Gandhi, MD 312-695-0287 mona-gandhi@northwestern.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00803842

Study ID Number: MEL-120407

ClinicalTrials.gov Identifier: NCT00803842

Health Authority: United States: Institutional Review Board