Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract

• Status: Completed
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective: To determine the Phase II doses and to evaluate the safety of administering bexarotene (Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers.

Secondary objectives: To evaluate the response rates, progression-free survival and overall survival of patients with advanced aerodigestive tract cancers treated with bexarotene (Targretin®) in combination with erlotinib (Tarceva™). To investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dartmouth-Hitchcock Medical Center
• Collaborators: Genentech, Inc.; Ligand Pharmaceuticals
• Treatments: Bexarotene; Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

• Pathological confirmation of advanced malignant aerodigestive tract tumo(lung, head and neck and esophagus)

• No known curative treatment.

• Age >18 years

• Karnofsky performance status ≥ 60%.

• Prior chemotherapy or radiotherapy is allowed.

• Fasting triglycerides equal or less than upper limit of normal

• Female patients and male patients with female partners of childbearing potential must agree to sexual abstinence or to practice effective contraception (recommended to be two reliable forms of non-hormonal contraception used simultaneously) during the entire period of Targretin capsule treatment and for at least one (1) month after treatment is discontinued. Male patients with female sexual partners who are pregnant, or possibly pregnant or who could become pregnant during the study must agree to use condoms during sexual intercourse during the entire period of Targretin capsule treatment and for at least one (1) month after the last dose of Targretin capsules.

• All patients must give informed consent indicating they are aware of the investigational nature of this treatment.

Exclusion Criteria:

• Organ dysfunction that precludes use of bexarotene or erlotinib:

• hepatic dysfunction, as evidenced by either:

• transaminase (SGOT or SGPT) > 2.5 X upper limit of normal (ULN) or > 5 X ULN if known liver metastases

• bilirubin > upper limit of normal

• renal dysfunction, as evidenced by calculated creatinine clearance < 30 ml/min

• A serious uncontrolled medical disorder or active infection which would impair their ability to receive study treatment will be excluded.

• Significant cardiac disease, including uncontrolled high blood pressure, unstable angina, congestive heart failure, myocardial infarction within the previous 3 months or serious cardiac arrhythmias will be excluded. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol will be excluded.

• Concurrent use of other anti-cancer investigational agents is not allowed

• Women who are pregnant or breast-feeding and women of childbearing potential or fertile males not using an adequate method of birth control will be excluded.

• Known hypersensitivity to bexarotene, erlotinib or other components of the capsules.

• Risk factor for pancreatitis (e.g., prior pancreatitis, uncontrolled hyperlipidemia,excessive alcohol consumption, uncontrolled diabetes mellitus, biliary tract 10 disease, and medications known to increase triglyceride levels or to be associated with pancreatic toxicity).

• Systemic anticancer therapy of any kind within 14 days prior to initiating study medications.

• Investigational therapy of any kind within 30 days prior to initiating study medications.

• Systemic vitamin A in doses exceeding 15,000 IU/day within 14 days prior to initiating study medications.

• Unwillingness or inability to minimize exposure to sunlight and artificial ultraviolet light while receiving the capsules.