Sorafenib, Cisplatin, and Etoposide in Treating Patients With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Trial of Sorafenib in Conjunction With Chemotherapy and as Maintenance Therapy in Extensive-Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: etoposide
* Drug: sorafenib tosylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib, Cisplatin, and Etoposide<br> | Drug: cisplatin<br>* 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.<br>Drug: etoposide<br>* 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.<br>Drug: sorafenib tosylate<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1-year | 
| 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 | reevaluated for response every 8 weeks | 
| 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. | Treatment repeats every 21 days for 4 courses in the absence of unacceptable toxicity. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extensive stage small cell lung cancer