Antineoplastic Agents

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Amino Acids

Erlotinib Hydrochloride

Bexarotene

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Level -I 200 mg/m2 Level I 300 mg/m2 Level II 300 mg/m2 Level III 400 mg/m2

Bexarotene (Targretin®)

Level -1 100mg Level I 100mg Level II 150mg Level III 150mg

Erlotinib (Tarceva™)

Konstantin H. Dragnev, MD

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.

This is a single institution open label dose-ranging trial. Consecutive, eligible patients presenting with the diagnosis of advanced aerodigestive tract malignancy are to be enrolled in this study. All eligible patients will receive continuous daily oral erlotinib (Tarceva™) with daily bexarotene oral capsules (Targretin®). The two agents will be taken at the same time. Three dose levels of daily bexarotene in combination with daily erlotinib will be studied.

Eligible patients will be entered in cohorts of three at each dose level. Doses will not be escalated over the course of treatment of an individual patient. If a single patient experiences grade 4 hematologic or ≥ grade 3 non-hematologic toxicity (excluding hyperlipidemia and nausea/vomiting), the next group of three patients will be entered at the same dose. A maximum of 6 evaluable patients will be enrolled at any one dose level. Dose escalation is performed after all patients (3 or 6) at the previous dose level have received treatment for 4 weeks. Treatment will continue until progression of disease, unacceptable adverse effects, or patient refusal. If grade 4 hematologic or ≥ grade 3 non-hematologic toxicity (excluding hyperlipidemia and nausea/vomiting) is observed in two or more patients on dose level 1, the next three patients (or six if similar toxicity develops in one of the first three patients) will receive dose level -1. If such toxicity is seen in two or more patients, the trial will be terminated. We anticipate the maximum accrual of 18 patients to this trial.

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

A Phase I Clinical Study of Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract

The purpose of this study is to evaluate the safety of daily oral administration of bexarotene in combination with erlotinib at three dose levels to patients with advanced aerodigestive tract cancer. At least 3 patients will be entered onto each dose level. Dose limiting toxicity is defined as grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity. The recommended Phase II dose is defined as the highest dose level of bexarotene oral capsules in combination with oral erlotinib that induces DLT in fewer than 33% of patients.

Response rates will be described using RECIST criteria wherever possible. Survival will be determined by the number of days from study entry until death or date of last known followup and will be analyzed using the Kaplan-Meier method. Time to progression is defined as the interval from the initiation of treatment to the occurrence of progression or to last contact, or to the start of other antitumor therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract	NCT01116622	Advanced, Malig...	Bexarotene (Tar... Erlotinib (Tarc...	18 Years -	Dartmouth-Hitchcock Medical Center
Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract	NCT01116622	Advanced, Malig...	Bexarotene (Tar... Erlotinib (Tarc...	18 Years -	Dartmouth-Hitchcock Medical Center
Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract	NCT01116622	Advanced, Malig...	Bexarotene (Tar... Erlotinib (Tarc...	18 Years -	Dartmouth-Hitchcock Medical Center

Spots Global Cancer Trial Database for bexarotene (targretin®)