Antineoplastic Agents

All Drugs and Chemicals

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.

Genentech, Inc.

Ligand Pharmaceuticals

Dartmouth-Hitchcock Medical Center

Neoplasms

All Conditions

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

A neck dissection of at least the ipsilateral sub-level 1B will be performed in all patients

neck dissection of at least the ipsilateral sub-level 1B

Thomas Robbins, M.D.

Hypothesis

1. The submandibular gland is not a lymphatic organ and usually remains uninvolved with head and neck cancer despite the presence of metastatic disease in the lymph nodes that surround it.
2. All the lymph nodes in the submandibular triangle can be removed without resection of the submandibular gland.

Study Design

A better understanding of the frequency of submandibular gland involvement may lead to refined treatment strategies for head and neck cancer, which can possibly spare removal of the submandibular gland and potentially improve the long term side effects from therapy.

Hypothesis

1. The submandibular gland is not a lymphatic organ and usually remains uninvolved with head and neck cancer despite the presence of metastatic disease in the lymph nodes that surround it.
2. All the lymph nodes in the submandibular triangle can be removed without resection of the submandibular gland.

Study Design

1. A prospective controlled study.
2. A neck dissection of at least the ipsilateral sub-level 1B will be performed in all patients. In case of oral cavity tumors, about 15 minutes prior to the surgery, 1ml of Lymphazurin® blue dye will be injected in 4 quadrants around the primary site. The dissection will be performed in 3 stages. In the first stage all lymph node groups that lie either lateral, anterior, posterior, superior, or inferior to the submandibular gland, but within anatomical boundaries of level 1B, will be dissected. The submandibular gland will be left intact for this portion of the procedure. Next, the submandibular gland will be removed. Lastly, any remaining fibrofatty tissue that lies deep to the submandibular gland within the confines of level IB will be removed. Each lymph node group, the submandibular gland, and the fibrofatty tissue lying deep to the submandibular gland, will be submitted for pathological assessment in separate containers.
3. The following end-points will be measured: the number of lymph nodes identified within each lymph node group, the number of lymph nodes located within the submandibular gland, and the number of lymph nodes within the fibrofatty contents lying deep to the submandibular gland. The presence or absence of carcinoma within each of the assessed nodes will be documented, as well as extracapsular spread.

A better understanding of the frequency of submandibular gland involvement may lead to refined treatment strategies for head and neck cancer, which can possibly spare removal of the submandibular gland and potentially improve the long term side effects from therapy.

Anatomical Relationship of Level IB Lymph Nodes to the Submandibular Gland in Cancer Patients

Prospective Study to Assess the Anatomical Relationship of Level IB Lymph Nodes to the Submandibular Gland in Patients With Carcinoma of the Upper Aerodigestive Tract

The number of head/ neck lymph nodes in pre-defined groups: Preglandular, Prevascular, Retrovascular, and Retroglandular as well as the number of nodes within the submandibular gland and within the fibrofatty contents lying deep to the submandibular gland.

Pathological detection of carcinoma within each of the dissected nodes reported as node groups.

Southern Illinois University

A neck dissection of at least the ipsilateral sub-level 1B will be performed in all patients.

Surgery

Age, Continuous

<=18 years

Between 18 and 79 years

>=80 years

Age, Customized

Sex: Female, Male

Not completed

submandibular gland excision

sublevel IB dissection

surgical bed inspection

Director of Clinical Trials

Preglandular nodal group-Right neck

Prevascular nodal group-Right neck

Retrovascular nodal group-Right neck

Retroglandular nodal group-Right neck

Preglandular nodal group-Left neck

Prevascular nodal group-Left neck

Retrovascular nodal group-Left neck

Retroglandular nodal group-Left neck

Submandibular nodes (Right or Left)

Nodes Deep to Submandibular gland (Right or Left)

A neck dissection of at least the ipsilateral sub-level 1B will be performed in all patients. The number of nodes for each nodal groups will be reported.

Surgical Lymph Node Groups

the Number of Lymph Nodes: 1. Identified Within Each Lymph Node Group, 2.Located Within the Submandibular Gland, and 3. Within the Fibrofatty Contents Lying Deep to the Submandibular Gland.

Preglandular nodal positivity right neck

Prevascular nodal positivity right neck

Retrovascular nodal positivity right neck

Retroglandular nodal positivity right neck

Preglandular nodal positivity left neck

Prevascular nodal positivity left neck

Retrovascular nodal positivity left neck

Retroglandular nodal positivity left neck

The Presence or Absence of Carcinoma Within Each of the Assessed Nodes Will be Documented, as Well as Extracapsular Spread.

Overall Study

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
Anatomical Relationship of Level IB Lymph Nodes to the Submandibular Gland in Cancer Patients	NCT00728130	Carcinoma	neck dissection...	18 Years -	Southern Illinois University

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