A Phase I/II Study of Bexarotene in Combination With ZD1839 (IRESSA®) in the Treatment of Non-Small Cell Lung Cancer

NCT00238628 | Completed Phase 1

• 4 other identifiers: LUN000580031IRUSIRES0436NCT00238628
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of Phase 1 of this study is to evaluate the safety of the combination regimen, bexarotene and ZD1839. Phase II will evaluate the median survival, time to disease progression, and toxicity.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (4)

• Overall response rate (RECIST CRITERIA), time to progression, toxicity

  Completed 9/2005

• Pharmacokinetic analysis

  Completed 12/2005

• Median survival

  Calculated Spring 2008

• Overall response rate (RECIST CRITERIA), time to progression, toxicity

  Final analysis Spring 2008

Interventions

Bexarotene DRUG

Iressa DRUG

Eligibility Criteria

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

You may qualify if:

• Patients may have non-measurable disease, or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan).
• Patients with asymptomatic or treated brain metastases will be eligible if they last received therapy (including steroids) \> 4 weeks from study entry and are felt to have a low likelihood of rapid deterioration from their brain metastases.
• Patients must have had at least 1 prior systemic therapy for NSCLC, or have shown intolerance to chemotherapy. Patients may not have received prior therapy with bexarotene, ZD1839, or erlotinib (Tarceva).
• At least 4 weeks must have elapsed from the time of major surgery and patients must have recovered from the effects of any significant procedure.
• A three week interval must have elapsed from the last dose of chemotherapy (30 days for investigational therapy), prior to beginning protocol therapy (6 weeks if nitrosoureas or mitomycin C). Palliative radiotherapy to bony sites of disease is allowed while on trial and up to time of enrollment provided patient has no significant side effects from the radiotherapy.
• Age \>= 18 years.
• Life expectancy \> 2 months.
• ECOG performance status 0-2.
• Women of childbearing potential must have a negative pregnancy test (serum ß HCG with a sensitivity of at least 50 mlU/L) within 7 days prior to initiation of treatment and must have used 2 reliable forms of effective contraception used simultaneously or have been sexually abstinent for at least 4 weeks prior to the negative pregnancy test through entry in the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Retinoid class agents are known teratogens.
• Female patients and male patients with female partners of childbearing potential must agree to sexual abstinence or to practice 2 reliable forms of effective contraception used simultaneously during the entire period of bexarotene capsule treatment and for at least 1 month after treatment is discontinued. Male patients must agree to use condoms if they have a female sexual partner who is, or may become, pregnant.
• Patients must have normal organ and marrow function as defined below:
• leukocytes \>= 3,000/ul
• absolute neutrophil count \>= 1,500/ul
• platelets \>= 100,000/ul

You may not qualify if:

• Thyroid disease
• Patients may not have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study and must have recovered from adverse events due to agents administered more than 4 weeks earlier. Palliative radiotherapy is allowed to bony sites of disease.
• Patients may not be receiving any other investigational agents or have received any within 30 days prior to day 1 of study.
• Patients with known symptomatic brain metastases are excluded from this clinical trial because of their poor prognosis, those with treated, asymptomatic brain metastases are eligible proved they have not required any therapy including steroids for at least 4 weeks.
• Patients with a history of allergic reactions or sensitivity attributed to compounds of similar chemical or biologic composition to bexarotene and ZD1839 are excluded.
• Patients with triglycerides or cholesterol levels which are not within normal limits or "normalized" with medication will be excluded.
• Patients will be excluded for uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with another active malignancy except for non-melanoma skin cancers are excluded.
• Pregnant or breastfeeding women are excluded.
• Patients with risk factors for pancreatitis are excluded such as a history of pancreatitis, significant alcohol consumption or other factors which are deemed to put them at high risk.
• Patients taking systemic vitamin A in doses exceeding 15,000 IU/day within 14 days of study entry will be excluded.
• Patients who are unwilling to minimize exposure to ultraviolet light (sunlight) while on bexarotene will be excluded.
• Patients MAY NOT TAKE GEMFIBROZIL while on study due to interactions with bexarotene
• Patients may not take phenytoin, carbamazepine, rifampicin, barbiturates, or St John's Wort while on the study.
• Patients with any evidence of clinically active interstitial lung disease will be excluded (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)

Sponsors & Collaborators

• Stanford University: lead
• Ligand Pharmaceuticals: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Bexarotene; Gefitinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

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

• Charlotte D Jacobs

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 11, 2005
• First Posted: October 13, 2005
• Study Start: April 1, 2004
• Primary Completion: April 1, 2005
• Study Completion: December 1, 2005
• Last Updated: July 20, 2010

Record last verified: 2010-07

Locations

US (1)