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

NCT01116622 | Completed Phase 1 DMC

• 1 other identifier: D0228
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)

Keywords

Aerodigestive; Targretin; Tarceva

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  When final patient is removed from study or at the discreation of the investigator

Secondary Outcomes (2)

• Response rates, progression-free survival and overall survival of patients with advanced aerodigestive

  When final patient is removed from study or at the discretion of the investigator

• Investigate the activity of this targeted combination therapy by evaluating changes in molecular markers from pre- and post-treatment buccal swab samples.

  When final patient is removed from study or at the discretion of the investigator

Study Arms (1)

Daily oral erlotinib and bexarotene capusles

EXPERIMENTAL

Open label dose-ranging trial

Drug: Bexarotene (Targretin®); Drug: Erlotinib (Tarceva™)

Interventions

Bexarotene (Targretin®) DRUG

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

Also known as: Targetin, LGD1069

Daily oral erlotinib and bexarotene capusles

Erlotinib (Tarceva™) DRUG

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

Daily oral erlotinib and bexarotene capusles

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead
• Genentech, Inc.: collaborator
• Ligand Pharmaceuticals: collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Interventions

Bexarotene; Erlotinib Hydrochloride

Intervention Hierarchy (Ancestors)

Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Konstantin H. Dragnev, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2010
• First Posted: May 5, 2010
• Study Start: April 1, 2003
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 18, 2023

Record last verified: 2014-11

Locations

US (1)