Gemcitabine Hydrochloride in Treating Patients With Locally Advanced Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT01893294
• Recruitment Status: Completed
• First Posted: July 9, 2013
• Last Update Posted: March 22, 2017
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Duct Cell Adenocarcinoma of the Pancreas; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer	Drug: gemcitabine hydrochloride; Drug: fluorouracil; Radiation: radiation therapy; Other: laboratory biomarker analysis	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Trial of Intra-tumoral Gemcitabine Therapy for Locally Advanced Pancreatic Carcinoma
• Actual Study Start Date: April 2013
• Actual Primary Completion Date: October 30, 2015
• Actual Study Completion Date: October 30, 2015

Arms and Interventions

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.	Drug: gemcitabine hydrochloride; Given IT; Other Names: dFdC; difluorodeoxycytidine hydrochloride; gemcitabine; Gemzar; Drug: fluorouracil; Given IV; Other Names: 5-fluorouracil; 5-Fluracil; 5-FU; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation; radiotherapy; therapy, radiation; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 4 weeks ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.)

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Michael Levy; Mayo Clinic

More Information

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01893294 History of Changes
• Other Study ID Numbers: MC1241; NCI-2013-00798 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MC1241 ( Other Identifier: Mayo Clinic ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: July 9, 2013
• Last Update Posted: March 22, 2017
• Last Verified: October 2015

Additional relevant MeSH terms:

Adenocarcinoma; Pancreatic Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; Fluorouracil; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs