Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-induced Rash

Condition(s) targeted: Non Small Cell Lung Cancer

Intervention: doxycycline (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Northwestern University

Official(s) and/or principal investigator(s):
Mario Lacouture, MD, Principal Investigator, Affiliation: Northwestern University

Overall contact:
Jennifer Hensley, MD, Phone: 312-695-0287, Email: j-hensley@northwestern.edu

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.

Official title: Evaluation of Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-induced Rash

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

Primary outcome: The primary objective of this study is to determine whether administration of doxycycline affects erlotinib PK

Secondary outcome: Secondarily, this study aims to investigate the relationship between erlotinib AUC and rash severity and to evaluate the efficacy of doxycycline in rash management.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Jennifer Hensley, MD, Phone: 312-695-0287, Email: j-hensley@northwestern.edu

Northwestern University, Chicago, Illinois 60611, United States; Recruiting
Jennifer Hensley, MD, Phone: 312-695-0287, Email: j-hensley@northwestern.edu
Mario Lacouture, MD, Principal Investigator

Starting date: October 2008
Last updated: October 15, 2009