Clinical trial NCT00803842: Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-induced Rash
Official title: Evaluation of Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-induced Rash
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Non Small Cell Lung Cancer
Keywords: erlotinib
rash
supportive care
Lead sponsor: Northwestern University
Sponsor class: OTHER
First posted: 2008-12-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: The primary objective of this study is to determine whether administration of doxycycline affects erlotinib PK
timeFrame: 14 days
Secondary outcomes:
measure: Secondarily, this study aims to investigate the relationship between erlotinib AUC and rash severity and to evaluate the efficacy of doxycycline in rash management.
timeFrame: 14 days
Other outcomes:
Locations:
Study officials:
affiliation: Northwestern University
name: Mario Lacouture, MD
role: PRINCIPAL_INVESTIGATOR
References: