Extensive Stage Small Cell Lung Cancer, Lung Metastases, Malignant Pleural Effusion, Recurrent Small Cell Lung Cancer
Conditions
Brief summary
AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This phase II study is studying how well giving AZD0530 works in treating patients with extensive-stage small cell lung cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine the 12-week progression-free survival rate of patients with extensive stage small cell lung cancer treated with AZD0530. SECONDARY OBJECTIVES: I. To determine the response rate in patients treated with this drug. II. To determine the overall survival and time-to-progression in patients treated with this drug. III. To determine the adverse events of AZD0530 in these patients IV. To determine the effect of AZD0530 treatment on levels of circulating tumor cells in these patients. V. To determine potential predictive markers of response in circulating tumor cells after treatment with this drug. VI. To evaluate the rate of tumor marker (i.e., circulating tumor cells) stabilization in patients treated with this drug. TERTIARY OBJECTIVES: I. To determine the effect of AZD0530 treatment on levels of circulating tumor cells. II. To determine potential predictive markers of response in circulating tumor cells after treatment with this drug. III. To evaluate the rate of tumor marker (i.e., circulating tumor cells) stabilization in patients treated with this drug. OUTLINE: Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are obtained at baseline and periodically during study to determine levels of circulating tumor cells for defined translational studies. After completion of study therapy, patients are followed periodically for up to 2 years.
Interventions
DRUGsaracatinib
Given orally
Sponsors
National Cancer Institute (NCI)
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 small cell lung cancer * No mixed histology * Extensive stage disease, defined as any of the following: * Metastatic disease outside the chest * Contralateral supraclavicular nodes or contralateral hilar nodes that cannot be included in a single radiation port * Cytologically confirmed malignant pleural effusion * Clinically significant effusions (e.g., symptomatic pleural effusion) must be drained prior to treatment * Previously untreated disease\* OR stable disease, partial response, or complete response ≤ 4 weeks after completion of one course (four 3-week courses) of standard platinum-based chemotherapy * No symptomatic, untreated, or uncontrolled CNS metastases * CNS metastases previously treated with whole brain radiotherapy allowed * ECOG performance status (PS) 0-2 * Life expectancy ≥ 12 weeks * WBC ≥ 3,000/mm³ * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin \> 9.0 g/dL * Total bilirubin \< 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * ALT and AST ≤ 3 times ULN (≤ 5 times ULN if liver involvement) * Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min * Proteinuria ≤ +1 on two consecutive dipsticks taken no less than 24hours apart * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective protection during and for up to 8 weeks after completion of study therapy * QTc interval ≤ 460 msec * No seizure disorder * No significant traumatic injury ≤ 4 weeks prior to registration * No clinically significant infection * No HIV-positivity * No second primary malignancy, except for carcinoma in situ of the cervix or nonmelanoma skin cancer, unless prior malignancy was diagnosed and treated ≥ 5 years with no subsequent evidence of recurrence * Patients with a history of low grade(Gleason score ≤ 6) localized prostate cancer will be eligible even if diagnosed \< 5 years prior to registration * No concurrent severe and/or uncontrolled medical conditions, including any of the following: * Cardiac arrhythmias * Angina pectoris uncontrolled with medication * Myocardial infarction within the past 3 months * Significant ECG abnormalities * Hypertension, labile hypertension, or history of poor compliance with anti-hypertensive medication * Congestive heart failure within the past 3 months, unless ejection fraction \> 40% * Interstitial pneumonia or extensive, symptomatic interstitial fibrosis of the lung * Poorly controlled diabetes * No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530 * No condition that impairs the ability to swallow AZD0530 tablets, including any of the following: * Gastrointestinal tract disease resulting in an inability to take oral medication or requiring IV alimentation * Prior surgical procedures affecting absorption of AZD0530 tablets * Active peptic ulcer disease * No serious condition that, in the opinion of the investigator, would compromise the patient's ability to complete the study * At least 4 weeks since prior major surgery (i.e., laparotomy) or open biopsy * At least 2 weeks since prior minor surgery * At least 4 weeks since any prior investigational ancillary therapy (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation) * At least 7 days since prior use of strong inhibitors of CYP3A4 and no concurrent use for up to 7 days after discontinuation of AZD0530 * Prior nonthoracic palliative radiotherapy allowed * Concurrent bisphosphonates for treatment of lytic metastatic bone disease allowed at the discretion of the treating physician * No concurrent prophylactic granulocyte colony-stimulating factor (i.e., G-CSF) * No concurrent products that stimulate thrombopoiesis * No concurrent St. John's wort * No other concurrent chemotherapy, immunotherapy, hormonal therapy,or radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate at 12 Weeks | 12 weeks | The progression-free survival (PFS) rate at 12 weeks will be estimated by calculating the number of patients that are alive and progression-free at 12 weeks post-registration divided by the total number of evaluable patients and multiplied by 100. All patients meeting the eligibility criteria who have signed a consent form, begun AZD0530 treatment, and are not lost to follow-up before 12 weeks, will be considered evaluable for the 12-week progression-free survival (PFS) rate. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is defined as having a new lesion or having at least a 20% increase in the sum of the longest diameter of target lesions from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From registration to death due to any cause, assessed up to 2 years | Overall Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. |
| Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart) | After every other 21-day cycle, up to 2 years. | Response was assessed using the RECIST v1.1 criteria. Patients were evaluated after every other cycle (after cycle 2, 4, 6, etc...) and when progression is suspected. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart.. |
| Progression Free Survival | From registration to documentation of disease progression or death, assessed up to 2 years | Progression Free Survival (PFS) is defined as the time from registration to documentation of disease progression or death, whichever occurs first. The distribution of time to progression will be estimated using the method of Kaplan-Meier. |
Countries
United States
Participant flow
Recruitment details
24 patients were enrolled from 13 medical clinics from February 5, 2008 to August 21, 2008.
Pre-assignment details
One patient cancelled prior to treatment initiation and is excluded in the analysis.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Saracatinib) Patients receive oral AZD0530 once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Blood samples are obtained at baseline and periodically during study to determine levels of circulating tumor cells for defined translational studies.
saracatinib : saracatinib 175mg given orally daily with re-treatment every 3 weeks | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | Treatment (Saracatinib) |
|---|---|
| Age, Continuous | 58 years |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 23 |
| serious Total, serious adverse events | 6 / 23 |
Outcome results
Primary
Progression-free Survival Rate at 12 Weeks
The progression-free survival (PFS) rate at 12 weeks will be estimated by calculating the number of patients that are alive and progression-free at 12 weeks post-registration divided by the total number of evaluable patients and multiplied by 100. All patients meeting the eligibility criteria who have signed a consent form, begun AZD0530 treatment, and are not lost to follow-up before 12 weeks, will be considered evaluable for the 12-week progression-free survival (PFS) rate. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progression is defined as having a new lesion or having at least a 20% increase in the sum of the longest diameter of target lesions from baseline.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Saracatinib) | Progression-free Survival Rate at 12 Weeks | 26 percentage of participants |
Secondary
Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart)
Response was assessed using the RECIST v1.1 criteria. Patients were evaluated after every other cycle (after cycle 2, 4, 6, etc...) and when progression is suspected. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart..
Time frame: After every other 21-day cycle, up to 2 years.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Saracatinib) | Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart) | Complete Response (CR) | 0 Participants |
| Treatment (Saracatinib) | Confirmed Tumor Response (Defined as Complete or Partial Response on 2 Consecutive Evaluations at Least 4 Weeks Apart) | Partial Response (PR) | 0 Participants |
Secondary
Overall Survival
Overall Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: From registration to death due to any cause, assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Overall Survival | 7.8 months |
Secondary
Progression Free Survival
Progression Free Survival (PFS) is defined as the time from registration to documentation of disease progression or death, whichever occurs first. The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Time frame: From registration to documentation of disease progression or death, assessed up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Progression Free Survival | 1.5 months |