Sunitinib and Gemcitabine in Treating Patients With Pancreatic Cancer or Other Solid Tumors

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of sunitinib and gemcitabine in treating patients with pancreatic cancer or other solid tumors. Sunitinib 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 hemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with gemcitabine may kill more tumor cells.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of sunitinib malate and gemcitabine hydrochloride in patients with adenocarcinoma of the pancreas or other solid tumors. II. Determine the toxicity of this regimen in these patients. OUTLINE: This is a dose-escalation study. Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 OR on days 1, 8, and 15. Patients also receive oral sunitinib malate once daily on days 1-21 OR days 1-28. Treatment repeats every 21 days OR every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and sunitinib malate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 patients may be treated at the recommended phase II dose (RPTD), which is generally the dose level below the maximally administered dose. After completion of study treatment, patients are followed for 30 days and then periodically thereafter.

Official Title
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A Phase I Study of Sunitinib Malate and Standard Infusion Gemcitabine in Solid Tumors

Conditions
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Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: sunitinib malate
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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Criteria: Histologically or cytologically confirmed pancreatic adenocarcinoma OR other solid tumor: Not amenable to curative therapy Previously untreated metastatic pancreatic adenocarcinoma allowed Measurable or evaluable disease No history of or known brain metastases, spinal cord compression, carcinomatous meningitis, or new evidence of brain or leptomeningeal disease on screening CT scan or MRI scan ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% Life expectancy >= 12 weeks Absolute neutrophil count >= 1,500/mm3 Platelet count >= 100,000/mm3 Hemoglobin >= 8.5 g/dL Bilirubin =< 1.5 mg/dL Creatinine normal OR creatinine clearance >= 60 mL/min AST and ALT =< 2.5 times upper limit of normal (ULN) (=< 5 times ULN if due to underlying disease) Calcium =< 12.0 mg/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy LVEF normal by MUGA scan or ECHO at baseline Deep venous thrombosis or pulmonary embolism allowed provided they are clinically stable and adequately treated No preexisting thyroid abnormality that results in the inability to maintain thyroid function in the normal range while using medication No history of allergic reactions attributed to compounds of similar chemical or biological composition to sunitinib malate No history of any of the following within the past 6 months: Myocardial infarction Ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation >= 3 beats in a row) Severe/unstable angina Severe peripheral vascular disease (i.e., claudication) Procedure on peripheral vasculature Coronary/peripheral artery bypass graft Cerebrovascular accident No history of any of the following within the past 6 months: Transient ischemic attack; Clinically significant bleeding requiring red blood cell transfusion No NYHA class III or IV heart disease: Patients with NYHA class II disease who are stable and on medication are eligible No ongoing cardiac dysrhythmias >= grade 2, atrial fibrillation of any grade, or any significant EKG abnormalities No hypertension that cannot be controlled by medications to a systolic blood pressure (BP) of < 140 mm Hg and diastolic BP of < 90 mm Hg No condition that impairs the ability to swallow and retain sunitinib malate tablets, including any of the following: Gastrointestinal tract disease resulting in an inability to take oral medication Requirement for IV alimentation Prior surgical procedures affecting absorption Active peptic ulcer disease No gastrointestinal perforation or intra-abdominal abscess within the past 28 days No serious nonhealing infection or bone fracture No other severe acute or chronic medical condition, psychiatric condition, or laboratory abnormality that would preclude study therapy May have received any number of prior systemic therapies More than 4 weeks since prior radiotherapy or surgery and recovered More than 4 weeks since other prior therapies and recovered Prior gemcitabine hydrochloride allowed No prior sunitinib malate or other therapy directed against VEGF, including any of the following: Sorafenib; Bevacizumab; Vatalanib; AZD2171; VEGF Trap; Investigational antiangiogenic therapy More than 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following: Ketoconazole Itraconazole Clarithromycin Erythromycin Diltiazem Verapamil Indinavir Ritonavir Nelfinavir Saquinavir Atazanavir Delavirdine More than 12 days since prior and no concurrent CYP3A4 inducers, including any of the following: Rifampin Rifabutin Carbamazepine Phenobarbital Phenytoin Hypericum perforatum (St. John's wort) Efavirenz Tipranavir No concurrent agents with proarrhythmic potential, including any of the following: Terfenadine Quinidine Procainamide Disopyramide Sotalol Probucol Bepridil Haloperidol Risperidone Indapamide Flecainide No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent treatment on another clinical trial: Participation in non-therapeutic clinical trials allowed QTc < 500 msec

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: Arm I<br>Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 OR on days 1, 8, and 15. Patients also receive oral sunitinib malate once daily on days 1-21 OR days 1-28. Treatment repeats every 21 days OR every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: sunitinib malate<br>* Given orally<br>* Other names: Sutent;Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate assessed by Response Evaluation Criteria for Solid Tumors (RECIST) |  | Up to 3 years | 
| Overall survival |  | Up to 3 years |