Lung Cancer
Conditions
Keywords
extensive stage small cell lung cancer
Brief summary
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sorafenib together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sorafenib together with cisplatin and etoposide works in treating patients with extensive-stage small cell lung cancer.
Detailed description
OBJECTIVES: * To evaluate the 1-year progression-free survival of patients with extensive-stage small cell lung cancer treated with sorafenib tosylate in combination with cisplatin and etoposide. * To evaluate the 1-year overall survival and response rate in these patients. * To evaluate the safety of these drugs in these patients. OUTLINE: This is a multicenter study. Patients receive cisplatin IV over 30-60 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral sorafenib tosylate twice daily beginning on day 1 of course 1 and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGcisplatin
Cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
DRUGetoposide
Etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
DRUGsorafenib tosylate
Oral sorafenib tosylate twice daily beginning on day 1 of course 1 and continuing for up to 1 year in the absence of disease progression or unacceptable toxicity.
Sponsors
National Cancer Institute (NCI)
Afshin Dowlati, MD
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
DISEASE CHARACTERISTICS: * Diagnosis of extensive-stage small cell lung cancer * No untreated brain metastases * No active symptoms related to brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Hemoglobin ≥ 9.0 g/dL * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement) * Creatinine ≤ 1.5 times ULN * INR \< 1.5 or PT/PTT normal * No history of cardiac disease, including any of the following: * NYHA class III-IV congestive heart failure * Unstable angina (i.e., anginal symptoms at rest) * Onset of angina within the past 3 months * Myocardial infarction within the past 6 months * No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy * No uncontrolled hypertension, defined as systolic blood pressure (BP) \> 150 mm Hg or diastolic BP \> 90 mm Hg, despite optimal medical management * No thrombolic or embolic events, such as cerebrovascular accident or transient ischemic attacks, within the past 6 months * No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within the past 4 weeks * No other hemorrhage/bleeding event ≥ CTCAE grade 3 within the past 4 weeks * No known HIV infection or chronic hepatitis B or C infection * No active clinically serious infection \> CTCAE grade 2 * No serious non-healing wound, ulcer, or bone fracture * No evidence or history of bleeding diathesis or coagulopathy * No significant traumatic injury within the past 4 weeks * No known or suspected allergy to sorafenib tosylate or to any other drug given during the study * No condition that would impair the patient's ability to swallow whole pills * No known malabsorption problem * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception * Male patients must use effective contraception during and for ≥ 3 months after completion of sorafenib tosylate PRIOR CONCURRENT THERAPY: * Prior radiotherapy to the brain allowed * No prior chemotherapy * More than 4 weeks since prior major surgery or open biopsy * No concurrent Hypericum perforatum (St. John's wort) or rifampin * Concurrent anti-coagulation treatment, such as warfarin or heparin, allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival(PFS) | 1-year | PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | 1-year | Overall survival is measured from the date of chemotherapy treatment (date of cycle 1 of induction chemotherapy) until death and censored at the date of last follow-up for survivors. |
| Response Rate | reevaluated for response every 8 weeks | The Response Evaluation Criteria in Solid Tumors (RECIST) were used to assess response to the treatment. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started |
| Safety | Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity. | Number of patients that experienced grade 3-4-5 treatment related toxicities. Toxicity was graded by the National Cancer Institute Common Terminology Criteria version 3.0. |
Countries
United States
Participant flow
Recruitment details
A total of 18 patients were enrolled into the trial from 3 sites between August 2008 and November 2011. Patients were recruited from University Hospitals Case Medical Center and Cleveland Clinic in Cleveland Ohio and Columbia Presbyterian in New York.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib, Cisplatin, and Etoposide Sorafenib, Cisplatin, and Etoposide for 4 cycles (months) during maintenance phase. If no disease progression continue with sorafenib for a maximum of 12 months. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Induction Phase | Adverse Event | 4 |
| Induction Phase | Death | 2 |
| Induction Phase | Lack of Efficacy | 5 |
| Induction Phase | Secondary Disease | 2 |
| Induction Phase | Withdrawal by Subject | 2 |
| Maintenance Phase | Adverse Event | 1 |
| Maintenance Phase | Lack of Efficacy | 2 |
Baseline characteristics
| Characteristic | Sorafenib, Cisplatin, and Etoposide |
|---|---|
| Age, Continuous | 63 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 17 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 9 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 | 17 / 17 |
| serious Total, serious adverse events | 14 / 17 |
Outcome results
Primary
Progression-free Survival(PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Time frame: 1-year
Population: Patients who received at least one dose of the study drug were considered evaluable for both toxicity and response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib, Cisplatin, and Etoposide | Progression-free Survival(PFS) | 5.1 months |
Secondary
Median Overall Survival
Overall survival is measured from the date of chemotherapy treatment (date of cycle 1 of induction chemotherapy) until death and censored at the date of last follow-up for survivors.
Time frame: 1-year
Population: Patients who received at least one dose of the study drug were considered evaluable for both toxicity and response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib, Cisplatin, and Etoposide | Median Overall Survival | 7.4 months |
Secondary
Response Rate
The Response Evaluation Criteria in Solid Tumors (RECIST) were used to assess response to the treatment. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Time frame: reevaluated for response every 8 weeks
Population: Patients who received at least one dose of the study drug were considered evaluable for both toxicity and response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib, Cisplatin, and Etoposide | Response Rate | Complete Response (CR) | 1 participants |
| Sorafenib, Cisplatin, and Etoposide | Response Rate | Partial Response (PR) | 7 participants |
| Sorafenib, Cisplatin, and Etoposide | Response Rate | Stable Disease (SD) | 1 participants |
| Sorafenib, Cisplatin, and Etoposide | Response Rate | Progressive Disease (PD) | 8 participants |
Secondary
Safety
Number of patients that experienced grade 3-4-5 treatment related toxicities. Toxicity was graded by the National Cancer Institute Common Terminology Criteria version 3.0.
Time frame: Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity.
Population: Patients who received at least one dose of the study drug were considered evaluable for both toxicity and response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib, Cisplatin, and Etoposide | Safety | 14 participants |