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

Phase 1
18 Years
Not Enrolling
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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

Inclusion Criteria


- Histologically or cytologically confirmed pancreatic adenocarcinoma OR other solid

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Smitha Krishnamurthi

Investigator Role:

Principal Investigator

Investigator Affiliation:

Case Western Reserve University


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

Related Keywords:

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



Case Western Reserve UniversityCleveland, Ohio  44106