Combination Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00089024

Recruitment Status : Unknown

Verified June 2010 by University of Nebraska.
Recruitment status was: Active, not recruiting

First Posted : August 5, 2004

Last Update Posted : June 3, 2010

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by:

University of Nebraska

Study Description

Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving combination chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with radiation therapy works in treating patients who may undergo surgery for locally advanced pancreatic cancer.

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Drug: fluorouracil Drug: gemcitabine hydrochloride Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase 2

Detailed Description:

OBJECTIVES:

Determine the antitumor and clinical benefit response to neoadjuvant chemoradiotherapy comprising gemcitabine, fluorouracil, leucovorin calcium, and oxaliplatin in patients with potentially resectable locally advanced adenocarcinoma of the pancreas.
Determine the toxic effects of this regimen in these patients.
Determine the achieved steady-state plasma levels of gemcitabine and fluorouracil in these patients and correlate these plasma levels with clinical toxicity associated with this regimen.
Determine the potential importance of polymorphic variations in genomic DNA of pertinent genes (whose protein products are targets of the antineoplastic drugs used in this study) on response to and toxicity of this regimen in these patients.
Determine the gene expression profiles of primary and metastatic pancreatic tumors before and after treatment with this regimen.

OUTLINE:

Neoadjuvant chemotherapy: Patients receive gemcitabine IV over 30 minutes and fluorouracil IV continuously over 24 hours on days 2 and 9, and leucovorin calcium orally on days 1 and 8 and IV on days 2 and 9. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Neoadjuvant chemoradiotherapy: Beginning on day 42, patients undergo chemoradiotherapy comprising oxaliplatin IV over 2 hours on days 42, 49, 56, 63, 70, and 77 and fluorouracil IV continuously on days 42-78 with external beam radiotherapy.
Surgery: Patients undergo surgical resection 42-56 days after completion of chemoradiotherapy.
Adjuvant chemotherapy: After post-operative recovery, patients receive 2 additional courses of gemcitabine, fluorouracil, and leucovorin calcium. If surgical resection is not possible, patients with stable or responsive disease resume gemcitabine, fluorouracil, and leucovorin calcium indefinitely in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase II Study Of Neo-Adjuvant Chemotherapy And Radiation In Patients With Locally Advanced Pancreatic Cancer
Study Start Date :	February 2004
Estimated Primary Completion Date :	December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pancreatic Cancer

U.S. FDA Resources

Arms and Interventions

Intervention Details:

2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 & 2; Repeat one 3-week cycle starting day 22

750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 & 2; Repeat one 3-week cycle starting day 22

20 mg/m5 PO (day 1) and 20 mg/m5 IV (day 2) weeks 1 and 2; Repeat one 3-week cycle starting day 22

48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5

Patients who have undergone surgical resection, after post-operative recovery, will receive two additional cycles of gemcitabine/5-FU/leucovorin. Patients will then be followed at 3 month intervals with a history and physical exam, CT scan of the chest/abdomen/pelvis, and tumor markers.

If surgical resection is not possible, patients with stable or responsive disease will resume gemcitabine/5-FU/leucovorin and continue on it indefinitely until disease progression provided the patient tolerates it and wishes to remain on therapy.

Restaging with repeat imaging studies will be performed four weeks after completion of the chemo-radiation. If no contraindication for surgical resection is identified, resection will be performed six to eight weeks after completing chemoradiation. At the time of surgical resection, an extensive examination of the abdomen will be performed to exclude the presence of metastatic disease. All operations will be performed with curative intent with resection of all gross tumor (ie R0 [negative margins] or R1 [positive microscopic margins]). Resection of adjacent involved organs or vascular structures will be performed as clinically indicated.

Eligible patients will receive an initial two cycles of chemotherapy with gemcitabine 750 (females) or 900 (males) mg/m5 over 30 minutes followed by a 24-hour infusion of fluorouracil 2700 mg/m5 on days 2 and 9 of a 21-day cycle . Calcium leucovorin 20 mg/m5 will be given orally on days 1 and 8 and by IV push on days 2 and 9 prior to the 5-FU. A window of -2 up to +7 days will be allowed to start planned cycles of therapy provided all other criteria to restart the new cycle has been met. Patients will require a central venous catheter (Port, Hickman or Groshong catheter) for the administration of 5-FU.

A re-staging CT scan, which will be obtained as part of the radiation simulation, will be used to assess any possible response to the initial two cycles of chemotherapy. Unless the patient has developed evidence of metastatic disease, chemoradiation will proceed. Patients who required no treatment delays will commence chemoradiation on day 42. If a one-week delay is needed before cycle 2 of neo-adjuvant chemotherapy can be delivered, the patient will begin chemoradiation on day 49 provided treatment-related toxicity has resolved. If cycle 2 could not be given (2 or more week delay for resolution of treatment-related toxicity), then chemoradiation will begin once toxicity has resolved (may be earlier than day 42).

Outcome Measures

Primary Outcome Measures :

Antitumor and clinical benefit response [ Time Frame: After 6 weeks of chemotherapy and then after 4 weeks of chemo-radiation. ]
Toxicity [ Time Frame: Weekly ]
Correlation of achieved steady-state plasma levels with clinical toxicity [ Time Frame: during protracted venous infusion ]
Correlative
Importance of polymorphic variations in genomic DNA of pertinent genes on response and toxicity [ Time Frame: Prior to starting therapy ]
Correlative
Gene expression profiles of primary and metastatic pancreatic tumors before and after treatment [ Time Frame: Before and after treatment ]
Correlative

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:	19 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of adenocarcinoma of the pancreas
- Locally advanced disease
Potentially resectable disease
- No early stage resectable disease
No evidence of distant metastases to the liver or peritoneal area according to imaging studies and laparoscopic staging

PATIENT CHARACTERISTICS:

Age

19 and over

Performance status

Karnofsky 60-100%

Life expectancy

Not specified

Hematopoietic

Absolute granulocyte count ≥ 2,000/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 2.0 mg/dL (in the absence of biliary obstruction)
- If biliary obstruction is present, patients must undergo biliary decompression
  - Bilirubin ≤ 3.0 mg/dL after biliary drainage has been established

Renal

Creatinine ≤ 1.6 mg/dL

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No serious uncontrolled cardiac arrhythmia

Other

Not pregnant or nursing
No uncontrolled illness
No active or ongoing infection requiring IV antibiotics
No marked intolerance to 5-fluoropyrimidines (i.e., fluorouracil, floxuridine, capecitabine, or fluorocytosine)
No allergy to sulfonamides, aspirin, or non-steroidal anti-inflammatory drugs
No allergy to platinum compounds or to antiemetics appropriate for administration in conjunction with study chemotherapy
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated noninvasive carcinoma

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy for pancreatic cancer

Endocrine therapy

Not specified

Radiotherapy

No prior abdominal radiotherapy

Surgery

Not specified

Other

No concurrent non-steroidal anti-inflammatory medication

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00089024

Locations


United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805

Sponsors and Collaborators

University of Nebraska

National Cancer Institute (NCI)

Investigators


Study Chair:	Jean L. Grem, MD	University of Nebraska

More Information


Responsible Party:	Jean L. Grem, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier:	NCT00089024 History of Changes
Other Study ID Numbers:	035-04 P30CA036727 ( U.S. NIH Grant/Contract ) UNMC-03504
First Posted:	August 5, 2004 Key Record Dates
Last Update Posted:	June 3, 2010
Last Verified:	June 2010

Keywords provided by University of Nebraska:


adenocarcinoma of the pancreas stage II pancreatic cancer stage III pancreatic cancer

Additional relevant MeSH terms:


Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine Fluorouracil Oxaliplatin Levoleucovorin	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 Antidotes Protective Agents

To Top