Extensive-Stage Small Cell Lung Cancer
Conditions
Brief summary
The goal of this study is to determine the progression-free survival rate in patients with extensive-stage small cell lung cancer who had achieved complete response, partial response, or stable disease with their previous platinum chemotherapy regimen, such as cisplatin or carboplatin in combination with etoposide or irinotecan. In addition, the safety and effectiveness of sunitinib will also be evaluated.
Detailed description
Despite a high initial response rate, all patients with extensive-stage small cell lung cancer treated with standard chemotherapy will develop disease progression, usually within one year of initial treatment. Therefore, prolonging progression-free survival in this disease is meaningful for clinical trials exploring agents such as sunitinib. Sunitinib is a drug that inhibits the biological pathway responsible for the growth and spread of cancer cells. For this reason, we believe that sunitinib maintenance therapy will delay or prevent recurrence and prolong survival. The goal of this study is to determine the progression-free survival rate in patients with extensive-stage small cell lung cancer who had achieved complete response, partial response, or stable disease with their previous platinum chemotherapy regimen, such as cisplatin or carboplatin in combination with etoposide or irinotecan. In addition, the safety and effectiveness of sunitinib will also be evaluated.
Interventions
DRUGsunitinib
Sunitinib will be given at 50 mg/day as a single agent for 4 consecutive weeks followed by a 2-week rest period to form a complete cycle of 6 weeks.
Sponsors
University of Michigan Rogel 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
* Histologically or cytologically confirmed extensive-stage SCLC. Extensive-stage is defined as disease that extends beyond one hemithorax and regional lymph nodes (ipsilateral or contralateral hilar, mediastinal, or supraclavicular lymph nodes), or with cytologically positive pleural effusion. * Patients who have completed platinum-based chemotherapy and demonstrated a complete response, partial response, or stable disease can be registered on the trial. A maximum of 4 cycles of induction chemotherapy is allowed. Patients must begin therapy within 28-42 days after day 1 of the 4th cycle of induction therapy and within 28 days of scans demonstrating stable disease or better. Prior palliative radiation therapy will be allowed as long as radiation was completed at least 1 week before starting protocol therapy. * Resolution of all acute toxic effects of prior chemotherapy or radiotherapy or surgical procedures to NCI CTCAE Version 3.0 grade 1. * Age \* 18 years with Southwest Oncology Group (SWOG) performance status of 0,1 or 2 (Appendix 2). * Adequate organ function as evidenced by the laboratory values listed in the protocol
Exclusion criteria
* Symptomatic or untreated brain or leptomeningeal metastases. Treated patients should be neurologically stable for at least 2 weeks after completion of appropriate therapy without the use of steroids. Patients currently on steroids are ineligible. * More than 4 cycles of induction chemotherapy. Patients will be eligible for if they have completed at least 2 cycles of platinum-based induction chemotherapy and they have exhibited a complete or partial response to therapy. Patients who have received less than 4 cycles of induction chemotherapy and have less than a partial response will not be eligible. * NCI CTCAE grade 3 hemorrhage within 4 weeks of starting the study treatment. * History of gross hemoptysis due to lung cancer. * Previous or concurrent malignancies, with the exception of adequately treated squamous cell or basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any other malignancy treated and in clinical remission for more than 3 years. * Major surgery or within 4 weeks of starting study treatment. * Any history of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF), cerebrovascular accident or transient ischemic attack, or pulmonary embolism. * Ongoing cardiac dysrhythmias * Hypertension that cannot be controlled by medications * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication. * Therapeutic anticoagulation with warfarin or heparin. * Serious concomitant medical illness, including, but not limited to, uncontrolled angina, myocardial infarction and/or stroke within 3 months, or HIV infection. * Acute or chronic liver disease * History of dementia, active psychiatric disorder or any other condition, considered by the treating physician to impair the patient's ability to take oral pills on a daily basis or comply with the protocol requirements. * Pregnant or lactating females. * Use of agents with proarrhythmic potential is not permitted during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate | 4 Months Post Treatment | The proportion of patients who are progression-free at 4 months after starting sunitinib. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | up to 4 months post treatment | Survival will be defined as the time from the first day of therapy to the date of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. Survival for induction therapy will be calculated from day 1 of first cycle of chemotherapy. Survival for post-induction therapy will be calculated from the date the patient starts sunitinib. |
| Percent of Patients With an Objective Response | 12 weeks (2 cycles) | Scans were performed every 2 cycles to evaluate for response/progression. Response was assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Patients would be considered to have an objective response if they experience CR (Complete Response - Disappearance of all clinical and radiological evidence of target lesions and/or non-target lesions) or PR (Partial Response - A 30% or greater decrease in the sum of LD of all lesions in reference to the baseline sum LD). |
| Number of Patients That Discontinue Drug Due to Toxicity | 20 weeks | Tolerability of Sunitinib will be evaluated by looking at the number of participants who discontinue drug due to toxicity. Toxicity was graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v.3.0. In the event of any CTC, version 3.0 drug-related grade 3 or 4 non-hematologic or grade 4 hematologic adverse event(s), drug should be held until the toxicity resolves to \< grade 1 and then the drug should be restarted at a one dose-level reduction. Recovery to acceptable levels of toxicity must occur within 4 weeks to allow continuation in the study. No more than 2 dose reductions are permitted for any patient. If further dose reduction is required, the patient must be removed from the study. |
Countries
United States
Participant flow
Recruitment details
16 subjects recruited from 7/19/2007 to 2/1/2010 at University of Michigan, Ann Arbor(lead site), and sub-sites: The University of Detroit's Karmanos Cancer Institute, WSU, Detroit; Weill Cornell Medical College, NY; and Roswell Park Cancer Institute, NJ
Pre-assignment details
Patients with histologically or cytologically documented Extensive-Stage Small Cell Lung Cancer (ES-SCLC) who had received no more than 4 cycles of frontline platinum plus etoposide chemotherapy and who demonstrated a response or stable disease were eligible. ES-SCLC was defined as disease extending beyond 1 hemothorax and regional lymph nodes.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib Maintenance Therapy Sunitinib 50 mg po QD × 28 days followed by a 14 day break every 42 days until disease progression or unacceptable toxicity. Treatment to begin 28-42 days after day 1 of the last cycle of induction chemotherapy to allow confirmation of response or disease stability with chemotherapy. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Sunitinib Maintenance Therapy |
|---|---|
| Age, Customized | 66 years |
| Performance status 0 | 5 participants |
| Performance status 1 | 10 participants |
| Performance status 2 | 1 participants |
| Region of Enrollment United States | 16 participants |
| Response to induction chemotherapy CR (complete response) | 3 participants |
| Response to induction chemotherapy PR (partial response) | 11 participants |
| Response to induction chemotherapy SD (stable disease) | 2 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 16 |
| serious Total, serious adverse events | 4 / 16 |
Outcome results
Primary
Progression Free Survival Rate
The proportion of patients who are progression-free at 4 months after starting sunitinib.
Time frame: 4 Months Post Treatment
Population: All 16 patients enrolled received a median of 4 weeks sunitinib maintenance therapy. 1 patient who discontinued requested no follow up and was censored from survival analysis. All survival endpoints were analyzed using the Kaplan-Meier method (Kaplan El, Meier P, Non-parametric Estimation from Incomplete Observations, J Am Stat Association, 1958)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Maintenance Therapy | Progression Free Survival Rate | 13 percentage of patients with PFS |
Secondary
Median Overall Survival
Survival will be defined as the time from the first day of therapy to the date of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. Survival for induction therapy will be calculated from day 1 of first cycle of chemotherapy. Survival for post-induction therapy will be calculated from the date the patient starts sunitinib.
Time frame: up to 4 months post treatment
Population: 15 participants in Sunitinib maintenance therapy (main study) were enrolled and were evaluable for this outcome measure. Although 16 patients were enrolled, one patient opted to discontinue therapy, refused further follow-up, and was therefore censored from survival analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib Maintenance Therapy | Median Overall Survival | 8.2 months |
Secondary
Number of Patients That Discontinue Drug Due to Toxicity
Tolerability of Sunitinib will be evaluated by looking at the number of participants who discontinue drug due to toxicity. Toxicity was graded according to the National Cancer Institute (NCI) Common Toxicity Criteria v.3.0. In the event of any CTC, version 3.0 drug-related grade 3 or 4 non-hematologic or grade 4 hematologic adverse event(s), drug should be held until the toxicity resolves to \< grade 1 and then the drug should be restarted at a one dose-level reduction. Recovery to acceptable levels of toxicity must occur within 4 weeks to allow continuation in the study. No more than 2 dose reductions are permitted for any patient. If further dose reduction is required, the patient must be removed from the study.
Time frame: 20 weeks
Population: All patients who received sunitinib maintenance therapy were evaluable for toxicity and tolerability analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Maintenance Therapy | Number of Patients That Discontinue Drug Due to Toxicity | 5 participants |
Secondary
Percent of Patients With an Objective Response
Scans were performed every 2 cycles to evaluate for response/progression. Response was assessed according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Patients would be considered to have an objective response if they experience CR (Complete Response - Disappearance of all clinical and radiological evidence of target lesions and/or non-target lesions) or PR (Partial Response - A 30% or greater decrease in the sum of LD of all lesions in reference to the baseline sum LD).
Time frame: 12 weeks (2 cycles)
Population: Patients who received at least 2 cycles of study therapy (maintenance sunitinib)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sunitinib Maintenance Therapy | Percent of Patients With an Objective Response | 0 percentage of participants |