Gemcitabine Hydrochloride in Treating Patients With Locally Advanced Pancreatic Cancer

Phase I Trial of Intra-tumoral Gemcitabine Therapy for Locally Advanced Pancreatic Carcinoma

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride in treating patients with locally advanced pancreatic cancer. 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 dividing.

Study Overview

• Status: Completed
• Conditions: Duct Cell Adenocarcinoma of the Pancreas; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: fluorouracil; Radiation: radiation therapy; Drug: gemcitabine hydrochloride

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerate dose (MTD) of intra-tumoral injection of gemcitabine (gemcitabine hydrochloride) when administered as a one time initial induction therapy in conjunction (=< 33 hours) prior to conventional multimodality treatment for locally advanced pancreatic cancer (LAPC).

SECONDARY OBJECTIVES:

I. To evaluate the initial and delayed toxicity associated with this treatment regimen.

OUTLINE: This is a dose-escalation study.

Patients receive gemcitabine hydrochloride intratumorally (IT) on day 1. Within 33 hours, patients receive standard chemotherapy comprising fluorouracil intravenously (IV) on days 1, 8, 15, 22, 29, and 36 and undergo standard radiation therapy 5 days a week for 6 weeks.

After completion of study treatment, patients are followed up for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytology proven pancreatic ductal carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0,1 or 2
• Absolute neutrophil count (ANC) >= 1500
• Platelets (PLT) >= 100,000
• Hemoglobin (HgB) > 9.0 g/dL
• Total bilirubin < 2.0 x upper limit of normal (ULN)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 5 x ULN
• Creatinine =< 1.5 mg/dL
• Negative pregnancy test done =< 14 days prior to registration, for women of childbearing potential only
• Provide informed written consent
• Imaging, a combination of at least two of the following (computed tomography [CT], magnetic resonance imaging [MRI], endoscopic ultrasound [EUS]) staging the pancreatic mass as "locally advanced"
• EUS clinically indicated for staging, and/or celiac neurolysis
• Resection declined by surgical staff based on designation of LAPC
• Willing to provide blood samples
• Willing to receive their standard multimodality therapy at Mayo Clinic, Rochester
• Willing to return to Mayo Clinic, Rochester during the observation phase

Exclusion Criteria:

• Any of the following:

  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• Any prior treatment (chemotherapy, radiation) for pancreatic cancer
• Other active malignancy =< 3 years prior to registration; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
• History of myocardial infarction =< 168 days (6 months), or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Prior pancreatic surgery
• Pancreatic tumor histology other than carcinoma (e.g. islet cell, lymphoma, etc.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (gemcitabine hydrochloride); Patients receive gemcitabine hydrochloride IT on day 1. Within 33 hours, patients receive standard chemotherapy comprising fluorouracil IV on days 1, 8, 15, 22, 29, and 36 and undergo standard radiation therapy 5 days a week for 6 weeks.	Other: laboratory biomarker analysis; Correlative studies; Drug: fluorouracil; Given IV; Other Names: 5-FU; 5-fluorouracil; 5-Fluracil; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation; Drug: gemcitabine hydrochloride; Given IT; Other Names: Gemzar; gemcitabine; dFdC; difluorodeoxycytidine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MTD of gemcitabine hydrochloride defined as the dose at which no more than 3 of 6 patients experience grade 3 or greater adverse events, as graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of immediate adverse events associated with this treatment, graded according to the NCI CTCAE version (v)3.0	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.	Within 72 hours of EUS
Incidence of delayed adverse events associated with this treatment, graded according to the NCI CTCAE v3.0	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.	4 weeks after completing standard systemic chemotherapy

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Levy, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2013
• Primary Completion (Actual): October 30, 2015
• Study Completion (Actual): October 30, 2015

Study Registration Dates

• First Submitted: July 2, 2013
• First Submitted That Met QC Criteria: July 2, 2013
• First Posted (Estimate): July 9, 2013

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Fluorouracil
• Other Study ID Numbers: MC1241 (Other Identifier: Mayo Clinic); P30CA015083 (U.S. NIH Grant/Contract); NCI-2013-00798 (Registry Identifier: CTRP (Clinical Trial Reporting Program))