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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Advanced, Malignant Aerodigestive Tract Tumor (Lung, Head and Neck and Esophagus)

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase II dose determination and evaulation of the safety of administering bexarotene(Targretin®) daily in combination with oral erlotinib (Tarceva™) to patients with advanced aerodigestive tract cancers.

Outcome Description:

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.

Outcome Time Frame:

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

Safety Issue:

No

Principal Investigator

Konstantin H. Dragnev, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dartmouth-Hitchcock Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

D0228

NCT ID:

NCT01116622

Start Date:

April 2003

Completion Date:

January 2013

Related Keywords:

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

Name

Location

Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756