A Phase I Study of Sunitinib Malate and Standard Infusion Gemcitabine in Solid Tumors
A Phase I Study of Sunitinib Malate and Standard Infusion Gemcitabine in Solid Tumors
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.
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.
Criteria:
Histologically or cytologically confirmed pancreatic adenocarcinoma OR other solid tumor:
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:
No history of any of the following within the past 6 months:
No NYHA class III or IV heart disease:
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:
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:
More than 12 days since prior and no concurrent CYP3A4 inducers, including any of the following:
No concurrent agents with proarrhythmic potential, including any of the following:
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent treatment on another clinical trial:
Participation in non-therapeutic clinical trials allowed