Sunitinib And Gemcitabine In Treating Patients With Pancreatic Cancer Or Other Solid Tumors

Study Overview

Sunitinib and Gemcitabine in Treating Patients With Pancreatic Cancer or Other 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.

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

DRUG: sunitinib malate
DRUG: gemcitabine hydrochloride

NCI-2009-00212
NCI-2009-00212 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
CDR0000539459
CASE 3206
CASE 3206 (OTHER Identifier) (OTHER: Case Western Reserve University)
7731 (OTHER Identifier) (OTHER: CTEP)
U01CA062502 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-04-18	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2014-02-21
First Submitted that Met QC Criteria 2007-04-18	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2014-02-24
First Posted (ESTIMATED) 2007-04-19	Results First Posted N/A	Last Verified 2013-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm I 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 dis	DRUG: sunitinib malate Given orally DRUG: gemcitabine hydrochloride Given IV

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Arm I

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 dis

DRUG: sunitinib malate

Given orally

DRUG: gemcitabine hydrochloride

Given IV

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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:

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:

QTc < 500 msec

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Smitha Krishnamurthi, Case Western Reserve University

Publications

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General Publications

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Clinical Trial Record