Sunitinib and Gemcitabine in Treating Patients With Pancreatic Cancer or Other Solid Tumors
Summary
RATIONALE: 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 chemotherapy, 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.
PURPOSE: 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.
Description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of sunitinib malate and gemcitabine hydrochloride in patients with adenocarcinoma of the pancreas or other solid tumors.
- 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.
PROJECTED ACCRUAL: A total of 37 patients will be accrued for this study.
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Pancreatic Cancer
Intervention
gemcitabine hydrochloride, sunitinib malate
Location
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland
Ohio
United States
44106-5065
Status
Active, not recruiting
Source
Case Comprehensive Cancer Center
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00462553
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Malate Dehydrogenase
An enzyme that catalyzes the conversion of (S)-malate and NAD+ to oxaloacetate and NADH. EC 1.1.1.37.
Malate Dehydrogenase (nadp+)
A light-activated enzyme that catalyzes the oxidation of (S)-malate to OXALOACETATE. It is involved in PYRUVATE metabolism and CARBON fixation.
Malate Synthase
An important enzyme in the glyoxylic acid cycle which reversibly catalyzes the synthesis of L-malate from acetyl-CoA and glyoxylate. This enzyme was formerly listed as EC 4.1.3.2.
Pancreatic Neoplasms
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).
Pancreatic Stellate Cells
Star-shaped, myofibroblast-like cells located in the periacinar, perivascular, and periductal regions of the EXOCRINE PANCREAS. They play a key role in the pathobiology of FIBROSIS; PANCREATITIS; and PANCREATIC CANCER.
Clinical Trials
RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, su...
RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether sunitinib malate is more effective than s...
Primary objective: to evaluate whether the addition of sunitinib prolongates the Progression-Free Survival (PFS) in patients with advanced pancreatic cancer receiving first-line gemcitabin...
This trial has two parts. The purpose of the first part of the trial is to determine the doses of 2 drugs, sunitinib malate and interferon alfa-2b, that can be given safely in combination....
RATIONALE: Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from div...
PubMed Articles
Combination of salinomycin and gemcitabine eliminates pancreatic cancer cells.
Previous research has documented that a subpopulation of pancreatic cancer cells, named cancer stem cells (CSCs), harbor stem cell-like properties. Here, we examined the efficacy of combined treatment...
Phase I trial of sunitinib and gemcitabine in patients with advanced solid tumors.
PURPOSE: Combining cytotoxic agents with bevacizumab has yielded significant benefits in a number of solid tumors. Combining small-molecule kinase inhibitors of VEGFR with chemotherapy has yet to demo...
INTRODUCTION: Gemcitabine is standard treatment for pancreatic cancer but has limited clinical benefit due to chemoresistance. Nuclear factor-kappaB (NF-κB) can promote chemoresistance and is therefo...
BACKGROUND: Receptor-associated protein 80 (RAP80) increases substantially in pancreatic cancer. The involvement of RAP80 in the chemoresistance of pancreatic cancer should be elucidated. AIMS: We inv...
Background Sorafenib, an inhibitor of B-raf, VEGFR2, and PDGFR-beta, has activity against pancreatic cancer in preclinical models. In a phase I trial of gemcitabine plus sorafenib, 57% of pancreatic c...
