Gemcitabine and Radiation Therapy in Treating Patients With Locally Advanced Upper Gastrointestinal Cancer

NCT ID: NCT00544193

Last Updated: 2015-06-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-12-31
• Study Completion Date: 2012-08-31

Brief Summary

RATIONALE: 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gemcitabine when given together with radiation therapy in treating patients with locally advanced upper gastrointestinal cancer.

Detailed Description

OBJECTIVES:

• To determine the feasibility of combining preoperative or intraoperative gemcitabine hydrochloride with intraoperative radiotherapy.
• To determine the tolerance of gemcitabine hydrochloride given concurrently with external-beam radiotherapy.
• To measure biochemical parameters in tumors that may correlate with the effectiveness of therapy.

OUTLINE: Patients receive gemcitabine hydrochloride IV 12-18 hours prior to planned surgery. All patients then undergo an exploratory laparotomy that may include tumor debulking, Whipple-type resection (pancreaticoduodenectomy), total pancreatectomy, gastrojejunostomy, total or partial gastrectomy, or cholecystectomy and en bloc resection depending on the extent of the disease. Patients with no metastatic disease beyond regional lymph nodes also undergo intraoperative radiotherapy.

Beginning 2-6 weeks after surgery, patients undergo external-beam radiotherapy (EBRT) once a day 5 days a week for up to 7 weeks. Patients also receive escalating doses of gemcitabine hydrochloride IV at the beginning of each week of EBRT.

Patients undergo tissue sample collection periodically for correlative studies. Samples are analyzed for thymidylate synthase (TS), ribonucleotide reductase (RR), excision-repair-cross-complementing (ERCC)-1 protein, deoxycytidine kinase mRNA. Biopsy tissues are also analyzed for gemcitabine triphosphate, dATP, and dCTP content. p53 status is assessed via immunohistochemistry and mRNA levels via quantitative polymerase chain reaction (PCR).

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then once a year thereafter.

Conditions

Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Pancreatic Cancer; Small Intestine Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

gemcitabine hydrochloride

Intervention Type: DRUG

polymerase chain reaction

Intervention Type: GENETIC

immunohistochemistry staining method

Intervention Type: OTHER

conventional surgery

Intervention Type: PROCEDURE

intraoperative radiation therapy

Intervention Type: RADIATION

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

PATIENT CHARACTERISTICS:

• Karnofsky performance status > 60%
• Life expectancy > 4 months
• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Serum creatinine < 2.0 mg/dL
• ALT < 3 x normal
• Bilirubin < 2 x normal
• Must be able to give voluntary informed consent
• No severe intercurrent illness that would make the patient inappropriate for laparotomy or otherwise inappropriate for treatment on protocol
• Prior history of malignancy allowed

PRIOR CONCURRENT THERAPY:

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C)
• Prior gemcitabine hydrochloride allowed

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen I. Shibata, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-97087

Identifier Type: -

Identifier Source: secondary_id

97087

Identifier Type: -

Identifier Source: org_study_id