Sorafenib Combined With Cisplatin and Etoposide or Carboplatin and Pemetrexed in Treating Patients With Metastatic Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Sorafenib and pemetrexed may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin, etoposide, and carboplatin, 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 cisplatin and etoposide or carboplatin and pemetrexed may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of sorafenib when given together with cisplatin and etoposide or carboplatin and pemetrexed in treating patients with metastatic solid tumors.

Detailed Description
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OBJECTIVES: Primary To determine the recommended phase II dose and maximum tolerated dose of sorafenib tosylate when administered in combination with cisplatin and etoposide or carboplatin and pemetrexed disodium in patients with metastatic solid tumors. Secondary To characterize the toxicities of these regimens in these patients. To evaluate the efficacy of these regimens in these patients, as measured by RECIST criteria or by tumor markers, if applicable (e.g., PSA, CA-125). To determine the pharmacokinetics of sorafenib tosylate when administered in combination with etoposide in these patients (samples are no longer being collected and studies are no longer being performed as of 1/8/09). OUTLINE: Patients are assigned to 1 of 2 treatment groups. Group 1: Patients receive cisplatin IV over 1 hour on day 2 of courses 1 and 2 and on day 1 of all subsequent courses; etoposide IV over 30 minutes on days 1-3; and oral sorafenib tosylate once or twice daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. Group 2: Patients receive carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Patients also receive sorafenib tosylate as in group 1. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. Patients in group 1 undergo blood sample collection on day 1 of courses 1 and 2 for pharmacokinetic studies (samples are no longer being collected and studies are no longer being performed as of 1/8/09). After finishing treatment, patients are followed at 30 days.

Official Title
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A Two Arm Phase I Trial of Sorafenib in Combination With Cisplatin/Etoposide or Carboplatin/Pemetrexed in Patients With Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: carboplatin
* Drug: cisplatin
* Drug: etoposide
* Drug: pemetrexed disodium
* Drug: sorafenib tosylate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed metastatic solid tumor Disease progressed during at least one standard therapy OR has a disease for which there is no standard therapy No squamous cell carcinoma of the lung Asymptomatic brain metastases allowed provided both of the following criteria are met: Brain metastases were treated ≥ 6 months ago Brain metastases are clinically stable without steroid treatment for 1 week No clinically relevant pleural effusions or ascites that cannot be controlled by drainage (group 2) PATIENT CHARACTERISTICS: ECOG performance status 0-1 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 INR < 1.5 or PT/PTT normal Creatinine clearance ≥ 45 mL/min Negative serum pregnancy test Fertile patients must use effective contraception during and for at least 2 weeks after completion of study treatment No New York Heart Association class III or IV congestive heart failure No unstable angina (anginal symptoms at rest) or new onset angina (within the past 3 months) No myocardial infarction within the past 6 months No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy No uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg, despite optimal medical management No known severe hypersensitivity to sorafenib tosylate or any its excipients, etoposide, pemetrexed disodium, cisplatin, or carboplatin No known HIV infection No chronic hepatitis B or C No active clinically serious infection > CTCAE grade 2 No thrombotic or embolic events, such as cerebrovascular accident or transient ischemic attacks, within the past 6 months No pulmonary hemorrhage or bleeding event ≥ CTCAE grade 2 within the past 4 weeks No other hemorrhage or bleeding event ≥ CTCAE grade 3 within the past 4 weeks No serious non-healing wound, ulcer, or bone fracture No evidence or history of bleeding diathesis or coagulopathy No condition that impairs the patient's ability to swallow whole pills No malabsorption problem, uncontrolled inflammatory bowel disease, or gastrointestinal disorder causing ≥ 5 bowel movements in a 24-hour period No significant traumatic injury within the past 4 weeks Able to take vitamin B12 supplementation and folic acid (group 2) PRIOR CONCURRENT THERAPY: More than 4 weeks since prior major surgery or open biopsy No more than 3 prior cytotoxic therapies for metastatic disease No concurrent St. John's wort or rifampin No non-steroidal anti-inflammatory drugs (NSAIDs) for 2 days before (5 days for long-acting NSAIDs), during, and for 2 days after pemetrexed disodium administration (group 2) Concurrent anticoagulation treatment with 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Patients receive cisplatin IV over 1 hour on day 2 of courses 1 and 2 and on day 1 of all subsequent courses; etoposide IV over 30 minutes on days 1-3; and oral sorafenib tosylate once or twice daily on days 1-21. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. | Drug: cisplatin<br>* Given IV<br>Drug: etoposide<br>* Given IV<br>Drug: sorafenib tosylate<br>* Given orally<br>|
| Experimental: Group 2<br>Patients receive carboplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Patients also receive sorafenib tosylate as in group 1. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression. | Drug: carboplatin<br>* Given IV<br>Drug: pemetrexed disodium<br>* Given IV<br>Drug: sorafenib tosylate<br>* Given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose and maximum tolerated dose of sorafenib tosylate when administered in combination with cisplatin and etoposide or carboplatin and pemetrexed disodium |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | 12 months | 
| Efficacy of treatment as measured by RECIST criteria or by tumor markers |  | 36 months | 
| Pharmacokinetics of sorafenib tosylate in combination with etoposide (samples are no longer being collected and studies are no longer being performed as of 1/8/09) |  | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific