Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-induced Rash - Full Text View

Sponsor:	Northwestern University
Information provided by:	Northwestern University
ClinicalTrials.gov Identifier:	NCT00803842

Purpose

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.

Condition	Intervention
Non Small Cell Lung Cancer	Drug: doxycycline

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Supportive Care
Official Title:	Evaluation of Erlotinib Pharmacokinetics During Doxycycline Treatment for Erlotinib-induced Rash

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Rashes

Drug Information available for: Doxycycline Doxycycline monohydrate Doxycycline Hyclate Doxycycline calcium Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

The primary objective of this study is to determine whether administration of doxycycline affects erlotinib PK [ Time Frame: 14 days ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2008
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00803842

Sponsors and Collaborators

Northwestern University

Investigators

Principal Investigator:

Mario Lacouture, MD

Northwestern University

More Information

No publications provided

Responsible Party:	Mario E. Lacouture, MD, Northwestern University
ClinicalTrials.gov Identifier:	NCT00803842 History of Changes
Other Study ID Numbers:	MEL-120407
Study First Received:	December 5, 2008
Last Updated:	January 19, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Northwestern University:

erlotinib
rash
supportive care

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Doxycycline
Doxycycline hyclate

Erlotinib
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2012