Extensive Stage Small Cell Lung Cancer, Limited Stage Small Cell Lung Cancer, Recurrent Small Cell Lung Cancer
Conditions
Brief summary
This phase II trial is studying how well dasatinib works in treating patients with relapse small cell lung cancer. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVE I. Determine the efficacy of dasatinib in patients with relapsed small cell lung cancer. SECONDARY OBJECTIVE II. Determine the objective response rate (complete and partial response) in patients treated with this drug. III. Determine the overall survival of patients treated with this drug. IV. Determine the toxicity of this drug in these patients. OUTLINE: Patients receive oral dasatinib twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at least every 3 months for 1 year and then every 6 months for 3 years.
Interventions
DRUGdasatinib
Given PO
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 (SCLC) (limited or extensive stage disease) * Progressive or recurrent disease after an initial response to first-line treatment with a platinum-based chemotherapy with or without concurrent definitive radiotherapy to the chest (chemotherapy must have been completed at least 90 days prior to documentation of relapse) * Measurable disease, defined as \>= 1 unidimensionally measurable lesion \>= 20 mm by conventional techniques OR \>= 10 mm by spiral CT scan * Lesions that are not considered measurable include the following: * Bone lesions * Leptomeningeal disease * Ascites * Pleural or pericardial effusion * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * Tumor lesions situated in a previously irradiated area, unless progression after radiotherapy is documented in these lesions * No known brain metastases (previously treated brain metastases allowed provided they are neurologically stable for \>= 4 weeks) * ECOG performance status 0-1 * Platelet count \>= 100,000/mm\^3 * Bilirubin =\< 1.5 times upper limit of normal (ULN) * Creatinine =\< 1.5 times ULN OR creatinine clearance \>= 60 mL/min * AST =\< 2.5 times ULN * Not pregnant or nursing * Negative pregnancy test * No significant cardiac disease, including any of the following: * New York Heart Association class III-IV heart disease * Myocardial infarction or ventricular tachyarrhythmia within the past 6 months * Prolonged QTc \> 480 msec (Fridericia correction) * Major conduction abnormality (unless a cardiac pacemaker is present) * No more than 1 prior chemotherapy regimen * No prior dasatinib or compounds of similar chemical composition or similar biologic therapeutic activity including, but not limited to, any inhibitors of SRC, BCR-ABL, c-KIT, EPHA2, or PDGFRB kinases * At least 2 weeks since prior definitive or palliative radiotherapy (prior radiotherapy allowed in the context of combined modality treatment with curative intent for limited stage disease; prophylactic cranial radiotherapy; or palliative radiotherapy initially or at relapse) * At least 2 weeks since prior surgery and recovered * At least 1 week since prior and no concurrent agents with proarrhythmic potential * At least 1 week since prior and no concurrent CYP3A4 inhibitors or inducers * At least 1 week since prior and no concurrent grapefruit concentrate * No concurrent palliative radiotherapy * No concurrent hormones or other chemotherapeutic agents, except steroids for adrenal failure, hormones for noncancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent chemotherapeutic or investigational agents * Fertile patients must use effective contraception during and for \>= 6 weeks after completion of study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 6 Week Progression Free Survival | 6 weeks | Percentage of patients who were alive and progression free at 6-weeks. The 6-week progression free survival was estimated using the Kaplan Meier method. Progressive Disease was defined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria as 20% increase in sum of longest diameter of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Time from registration to progression (up to 3 years) | PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure. |
| Response to Therapy | Assessed every 2 cycles (up to 3 years) | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; * Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; * Stable Disease (SD): small changes that do not meet above criteria. |
| Overall Survival | Time from registration to death (up to 3 years) | Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method. |
| Number of Participants With Grade 3 or Higher Adverse Events | Assessed during treatment | The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 was used to evaluate toxicity. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death. |
Countries
United States
Participant flow
Recruitment details
Between July 2007 and December 2008, 45 participants were recruited.
Pre-assignment details
One(1) participant cancelled before receiving any protocol related therapy and 1 participant was deemed ineligible. All participants receiving treatment were analyzed for adverse events and only eligible (43) participants were analyzed for al other endpoints.
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib Pts receive oral dasatinib 70 mg twice daily | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 1 |
Baseline characteristics
| Characteristic | Dasatinib |
|---|---|
| Age, Continuous | 64 years |
| ECOG Performance Status 0 - Fully Active | 12 participants |
| ECOG Performance Status 1 - Ambulatory, restricted strenuous activity | 31 participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 44 |
| serious Total, serious adverse events | 14 / 44 |
Outcome results
Primary
6 Week Progression Free Survival
Percentage of patients who were alive and progression free at 6-weeks. The 6-week progression free survival was estimated using the Kaplan Meier method. Progressive Disease was defined by the Response Evaluation Criteria In Solid Tumors (RECIST) criteria as 20% increase in sum of longest diameter of target lesions.
Time frame: 6 weeks
Population: All eligible participants were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | 6 Week Progression Free Survival | 43 percentage of participants |
Secondary
Number of Participants With Grade 3 or Higher Adverse Events
The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 was used to evaluate toxicity. Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.
Time frame: Assessed during treatment
Population: All 44 participants who received treatment were analyzed (including ineligible participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | Number of Participants With Grade 3 or Higher Adverse Events | 12 participants |
Secondary
Overall Survival
Overall survival (OS) was defined as the time from registration to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method.
Time frame: Time from registration to death (up to 3 years)
Population: All eligible participants were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib | Overall Survival | 17 weeks |
Secondary
Progression Free Survival (PFS)
PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.
Time frame: Time from registration to progression (up to 3 years)
Population: All eligible participants were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib | Progression Free Survival (PFS) | 5.9 weeks |
Secondary
Response to Therapy
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: * Complete Response (CR): disappearance of all target lesions; * Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; * Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; * Stable Disease (SD): small changes that do not meet above criteria.
Time frame: Assessed every 2 cycles (up to 3 years)
Population: All eligible participants were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Response to Therapy | Complete Response | 0 participants |
| Dasatinib | Response to Therapy | Partial Response | 0 participants |
| Dasatinib | Response to Therapy | Stable Disease | 7 participants |
| Dasatinib | Response to Therapy | Progression | 28 participants |
| Dasatinib | Response to Therapy | Inadequately assessed | 8 participants |