Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, NSCLC, Lung Cancer, ZD6474, Zactima, Vandetanib, BATTLE Program
Brief summary
Primary Objective: * 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. Secondary Objectives: * Determine the overall response rate * Determine the overall survival * Determine the time to disease progression * Assess the safety/toxicity of the study treatment * Assess biomarker modulation in the tumor tissue and serum samples from the treatment * Assess plasma and intra-tumor concentrations of study treatment
Detailed description
ZD6474 is designed to block the formation of new blood vessels. The growth of new blood vessels is called angiogenesis. Angiogenesis is thought to be important for the growth of tumors beyond a small size. Researchers want to find out if ZD6474 will limit new blood vessel growth in the tumor and starve the tumor by limiting blood flow to it. In order to enroll in this study, you must also be enrolled in Protocol 2005-0823: A Biomarker-integrated study in Chemorefractory Patients with Advanced Non-Small Cell Lung Cancer. Protocol 2005-0823 is the screening study in a group of studies called the BATTLE program. Participants in Protocol 2005-0823 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 treatment study. While on study, you will take ZD6474 by mouth each morning. ZD6474 is swallowed as a whole tablet. The tablet should not be chewed, crushed, or divided and should be taken with 8 ounces of water and a small amount of food to lessen stomach discomfort. You should take ZD6474 at about the same time every day. Four (4) weeks is considered 1 treatment cycle. If you miss a dose and are unable to take the missed dose on the same day, you should take the next scheduled dose and the missed dose will not be made up. The dose of study medication may be repeated if vomiting occurs within 30 minutes of taking the study medication. You will have routine blood tests (about 2 teaspoons) at Weeks 1, 2, 4, 8, 12, then every 4 weeks after that. You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart) at Weeks 1, 2, 4, 8, 12, then every 3 months after that. Every 4 weeks, your complete medical history will be recorded and you will have a physical exam, including measurement of vital signs (blood pressure, heart rate, temperature, and breathing rate), a performance status evaluation, and weight. You will also have a routine urine test and your study doctor will 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, you will have blood drawn (about 1-2 teaspoons) to check your blood clotting function every week. You will be asked to bring your unused medication to each clinic visit. You may continue receiving ZD6474 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, and/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, chest x-ray, ECG, 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. You have the right to leave the study at any time. If you choose to stop participating in this study, you should contact the study chair and/or research nurse. This is an investigational study. ZD6474 is an investigational drug that has been approved by the FDA for research use only. Up to 72 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.
Interventions
DRUGZD6474
300 mg by mouth daily for 28 Days.
Sponsors
United States Department of Defense
AstraZeneca
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 Eastern Cooperative Oncology Group (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, White Blood Count (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 times the upper limit of normal, and alkaline phosphatase, Alanine aminotranferease (ALT) or aspartate aminotransferase (AST) \</= 2.5 times 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 prothrombin time (PT) \< 1.5 times 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. Re-imaging performed after 2 weeks, upon completion of radiation therapy. 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 childbearing 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 |
|---|---|---|
| 8-Week Disease Control Rate (Complete Response, Partial Response and Stable Disease) | Baseline to 8 Weeks | The disease control rate (DCR) is the percentage of patients without progression at 8 weeks. Disease control rate defined as: Complete Response (CR): Disappearance of all non-target/target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 8 Week Progression-Free Survival | Every 8 weeks till disease progression. | Progression-free survival (PFS) was estimated using Kaplan-Meier method. PFS was defined as time from start of treatment to disease progression. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: November 2006 to February 2010. All participants recruited at The University of Texas MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| ZD6474 ZD6474 300 mg by mouth daily. | 54 |
| Total | 54 |
Baseline characteristics
| Characteristic | ZD6474 |
|---|---|
| Age, Continuous | 61 years |
| Age, Customized <=50 years | 11 participants |
| Age, Customized >70 years | 9 participants |
| Age, Customized Between 51 and 60 years | 15 participants |
| Age, Customized Between 61 and 70 years | 19 participants |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 54 |
| serious Total, serious adverse events | 54 / 54 |
Outcome results
Primary
8-Week Disease Control Rate (Complete Response, Partial Response and Stable Disease)
The disease control rate (DCR) is the percentage of patients without progression at 8 weeks. Disease control rate defined as: Complete Response (CR): Disappearance of all non-target/target lesions and normalization of tumor marker level. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.
Time frame: Baseline to 8 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ZD6474 | 8-Week Disease Control Rate (Complete Response, Partial Response and Stable Disease) | 33 percentage of participants |
Secondary
8 Week Progression-Free Survival
Progression-free survival (PFS) was estimated using Kaplan-Meier method. PFS was defined as time from start of treatment to disease progression.
Time frame: Every 8 weeks till disease progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ZD6474 | 8 Week Progression-Free Survival | 1.81 months |