Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01116622|
Recruitment Status : Completed
First Posted : May 5, 2010
Last Update Posted : November 13, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)||Drug: Bexarotene (Targretin®) Drug: Erlotinib (Tarceva™)||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Clinical Study of Erlotinib (Tarceva) and Bexarotene (Targretin) Oral Capsules in Advanced Cancers of the Aerodigestive Tract|
|Study Start Date :||April 2003|
|Actual Primary Completion Date :||April 2014|
|Actual Study Completion Date :||April 2014|
Experimental: Daily oral erlotinib and bexarotene capusles
Open label dose-ranging trial
Drug: Bexarotene (Targretin®)
Level -I 200 mg/m2 Level I 300 mg/m2 Level II 300 mg/m2 Level III 400 mg/m2
Other Name: Targetin, LGD1069
Drug: Erlotinib (Tarceva™)
Level -1 100mg Level I 100mg Level II 150mg Level III 150mg
- Phase II dose determination and evaluation of the safety of administering bexarotene(Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers. [ Time Frame: When final patient is removed from study or at the discreation of the investigator ]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, progression-free survival and overall survival of patients with advanced aerodigestive [ Time Frame: When final patient is removed from study or at the discretion of the investigator ]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.
- Investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples. [ Time Frame: When final patient is removed from study or at the discretion of the investigator ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01116622
|United States, New Hampshire|
|Dartmouth-Hitchcock Medical Center|
|Lebanon, New Hampshire, United States, 03756|
|Principal Investigator:||Konstantin H. Dragnev, MD||Dartmouth-Hitchcock Medical Center|