Lung Cancer
Conditions
Keywords
Lung Cancer, Non-Small Cell Lung Cancer, NSCLC, Erlotinib, Tarceva, Bexarotene, Targretin, OSI-774, Battle Program
Brief summary
The goal of this clinical research study is to evaluate the effectiveness of Tarceva® (OSI-774, erlotinib hydrochloride) in combination with Targretin® (bexarotene) in treating NSCLC. The safety of this treatment will also be studied, as well as the treatment's effect on different cells in the body and the participants' overall response.
Detailed description
Erlotinib hydrochloride is designed to help block the activity of an enzyme that is believed to play an important role in cell growth. Researchers want to find out if blocking these enzymes will slow tumor growth. Bexarotene is designed to control cancer cell growth and division. In order to enroll in this study, you must also be enrolled in Protocol 2005-0823 (NCT00409968): A Biomarker-integrated study in Chemorefractory Patients with Advanced Non-Small Cell Lung Cancer. Protocol 2005-0823 (NCT00409968) is the screening study in a group of studies called the BATTLE program. Participants in Protocol 2005-0823(NCT00409968) are assigned to one of the research studies. The results of your tumor analysis helped the study doctor determine to assign you to this particular research study. While on study, you will take erlotinib hydrochloride and bexarotene by mouth once a day. Erlotinib hydrochloride tablets should be taken preferably in the morning 1 hour before or 2 hours after a meal with no more than 7 ounces of water. If you forget to take a dose, the last missed dose should be taken as soon as you remember, as long as it is at least 12 hours before the next dose is due to be taken. The next day, you should take the scheduled dose at the usual time. Bexarotene capsules should be taken with or immediately after a meal. If you miss a dose, take it as soon as possible, with food. However, if it is nearly time for your next dose, skip the missed dose and continue your dose schedule as before. Every attempt should be made to keep from vomiting the medication for at least 30 minutes after taking it. For example, if you feel nauseated before or after taking the medication, anti-nausea medications should be used. The erlotinib hydrochloride tablets and bexarotene capsules should be stored at room temperature. Bexarotene capsules should not be stored near heating devices, high temperatures or humidity, or where children or pets have access to them. Bexarotene capsules should be protected from sunlight. Every 4 weeks (1 cycle) your medical history will be recorded and you will have a physical exam, including measurement of vital signs (blood pressure, pulse, temperature, and breathing rate) and weight. You will have routine blood tests (about 2 teaspoons) and a performance status evaluation (questions about your ability to perform everyday activities). You will have blood drawn (about 1-2 teaspoons) to check you thyroid function. You will also have blood drawn (about 1-2 teaspoons) to check your lipid profile weekly for the first 4 weeks and then every cycle after that. Your study doctor will also ask you about any medications you are taking and your smoking history. Every 2 cycles, your tumor will be evaluated by chest x-ray and computed tomography (CT) or magnetic resonance imaging (MRI) scans to evaluate the status of the disease. If you are taking Coumadin® (warfarin), you will have blood drawn (about 1-2 teaspoons) to check your blood clotting function weekly for the first 5 weeks of treatment and then every cycle after that. You may continue receiving erlotinib hydrochloride and bexarotene for as long as the cancer responds to study treatment. Your doctor may decide to take you off this study if you experience intolerable side effects, your medical condition gets worse, or you are unable to comply with study requirements. If you stop study treatment, you may be able to enroll in 1 of the remaining 3 protocols of the BATTLE program. After you have stopped taking the study treatment, you will have a physical exam, including measurement of vital signs. Blood (about 2 teaspoons) and urine will be collected for routine tests. You will also have blood drawn (about 1-2 teaspoons) to check your blood clotting function. You will have a performance status evaluation, a chest x-ray, and a CT or MRI scan. Following this evaluation, you will be contacted by telephone every 3 months for up to 3 years, to see how you are doing. This is an investigational study. Erlotinib hydrochloride is approved by the FDA for treatment of NSCLC in patients who have relapsed. Bexarotene is approved by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Their use together in this study is investigational. Up to 72 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.
Interventions
DRUGBexarotene
400 mg/m\^2 by mouth daily x 28 Days
DRUGErlotinib
150 mg by mouth daily x 28 Days
Sponsors
United States Department of Defense
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration. 2. The patient has a diagnosis of either stage IIIB, stage IV, or advanced, incurable NSCLC, and failed at least one front-line metastatic NSCLC chemotherapy regimen. (Patients who have failed adjuvant or locally advanced therapy within 6 months are also eligible to participate in study). 3. The patient has uni-dimensionally measurable NSCLC. 4. Karnofsky performance status \>/= 60 or ECOG performance status 0-2 5. The patient has biopsy accessible tumor. 6. The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) \>/= 1,500/mm\^3, platelet count \>/= 100,000/mm\^3, WBC \>/= 3,000/ mm\^3, and hemoglobin \>/= 9 g/dL. 7. The patient has adequate hepatic function as defined by a total bilirubin level \</= 1.5 X the upper limit of normal, and alkaline phosphatase, AST or ALT \</= 2.5 X the upper limit of normal. 8. The patient has adequate renal function as defined by a serum creatinine level \</= 1.5 mg/dL or a calculated creatinine clearance of \>/= 60cc/minute. 9. The patient has PT \< 1.5 x upper limit of normal 10. If patient has brain metastasis, they must have been stable (treated or asymptomatic) for at least 4 weeks after radiation if treated with radiation and not have used steroids for at least 1 week. 11. The patient is \>/= 18 years of age. 12. The patient has signed informed consent. 13. The patient is eligible if disease free from a previously treated malignancy, other than a previous NSCLC, for greater than two years. Patients with a history of prior basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix are exempt from exclusion. 14. Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Childbearing potential will be defined as women who have had menses within the past 12 months, who have not had tubal ligation or bilateral oophorectomy. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately. The patient, if a man, agrees to use effective contraception or abstinence. 15. Subject must be considered legally capable of providing his or her own consent for participation in this study.
Exclusion criteria
1. The patient has received prior investigational therapy, chemotherapy, surgery, or radiotherapy within 4 weeks of initiating study drug 2. The patient has undergone prior thoracic or abdominal surgery within 28 days of study entry, excluding prior diagnostic biopsy. 3. The patient has received radiation therapy to the measurable tumor within 6 months. Patients are allowed to have local irradiation for the management of tumor-related symptoms (bones, brain). However, if a patient has active new disease growing in the previously irradiated site, the patient will be eligible to participate in the study. 4. The patient has a significant medical history or unstable medical condition (unstable systemic disease: congestive heart failure (New York Heart Association Functional Classification class II or worse), recent myocardial infarction within 3 months, unstable angina, active infection (i.e. currently treated with antibiotics), uncontrolled hypertension). Patients with controlled diabetes will be allowed. Patient must be able to undergo procedure for tissue acquisition. 5. The patient has uncontrolled seizure disorder, active neurologic disease, or neuropathy \>/= grade 2. Patients with meningeal or CNS involvement by tumor are eligible for the study if the above
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type | 8 weeks | The primary objective is to determine the 8 week progression-free survival rate (i.e. disease control rate) in patients with advanced NSCLC who have failed at least one prior chemotherapy regimen. A radiologist independently assessed DC, which was defined as a complete or partial response or stable disease according to the RECIST(29) at the end of 8 weeks (start of treatment to end of second treatment cycle). PFS was assessed from the date of randomization to the earliest sign of disease progression or death from any cause. OS was assessed from the date of randomization until death from any cause. Tumor response was assessed every 8 weeks until disease progression. Toxicity was assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. |
Countries
United States
Participant flow
Recruitment details
Thirty-seven (37) patients were registered into this trial. All thirty-seven (37) patients were eligible to participate in this trial.
Pre-assignment details
Participants enrolling in this study must first be enrolled in the BATTLE umbrella protocol and must meet all of the BATTLE eligibility criteria. Participants enrolled in the BATTLE program will be assigned to a specific biomarker-integrated study based on the adaptive randomization model.
Participants by arm
| Arm | Count |
|---|---|
| Bexarotene + Erlotinib Bexarotene 400 mg/m\^2 by mouth daily x 28 Days. Erlotinib 150 mg by mouth daily x 28 Days.
Bexarotene: 400 mg/m\^2 by mouth daily x 28 Days
Erlotinib: 150 mg by mouth daily x 28 Days | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Bexarotene + Erlotinib |
|---|---|
| Age, Continuous | 62 years |
| Age, Customized <=50 years | 6 Participants |
| Age, Customized 51-60 years | 11 Participants |
| Age, Customized 61-70 years | 11 Participants |
| Age, Customized >70 years | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 37 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 37 |
| other Total, other adverse events | 13 / 37 |
| serious Total, serious adverse events | 8 / 37 |
Outcome results
Primary
Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type
The primary objective is to determine the 8 week progression-free survival rate (i.e. disease control rate) in patients with advanced NSCLC who have failed at least one prior chemotherapy regimen. A radiologist independently assessed DC, which was defined as a complete or partial response or stable disease according to the RECIST(29) at the end of 8 weeks (start of treatment to end of second treatment cycle). PFS was assessed from the date of randomization to the earliest sign of disease progression or death from any cause. OS was assessed from the date of randomization until death from any cause. Tumor response was assessed every 8 weeks until disease progression. Toxicity was assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0.
Time frame: 8 weeks
Population: The primary end point was the 8-week DCR \[complete or partial response or stable disease via Response Evaluation Criteria in Solid Tumors (RECIST, which we compared with the historical 30% DCR estimate in similar patients. Treatment efficacy (a positive finding) was defined as \>0.80 probability of achieving\>30% DCR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib + Bexatrtene | Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type | EGFR | 11 participants |
| Erlotinib + Bexatrtene | Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type | KRAS/BRAF | 1 participants |
| Erlotinib + Bexatrtene | Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type | VEGF/VEGFR-2 | 0 participants |
| Erlotinib + Bexatrtene | Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type | RXR/Cyclin D1 | 1 participants |
| Erlotinib + Bexatrtene | Number of Participants With 8-week Progression-Free Survival (i.e. Disease Control Rate) Stratified by Cancer Mutation Type | None | 5 participants |