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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2010 by University of Nebraska.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
University of Nebraska
ClinicalTrials.gov Identifier:
NCT00089024
First received: August 4, 2004
Last updated: June 1, 2010
Last verified: June 2010

August 4, 2004
June 1, 2010
February 2004
December 2013   (final data collection date for primary outcome measure)
  • Antitumor and clinical benefit response [ Time Frame: After 6 weeks of chemotherapy and then after 4 weeks of chemo-radiation. ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Weekly ] [ Designated as safety issue: Yes ]
  • Correlation of achieved steady-state plasma levels with clinical toxicity [ Time Frame: during protracted venous infusion ] [ Designated as safety issue: Yes ]
    Correlative
  • Importance of polymorphic variations in genomic DNA of pertinent genes on response and toxicity [ Time Frame: Prior to starting therapy ] [ Designated as safety issue: Yes ]
    Correlative
  • Gene expression profiles of primary and metastatic pancreatic tumors before and after treatment [ Time Frame: Before and after treatment ] [ Designated as safety issue: No ]
    Correlative
Not Provided
Complete list of historical versions of study NCT00089024 on ClinicalTrials.gov Archive Site
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Combination Chemotherapy, and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer
A Phase II Study Of Neo-Adjuvant Chemotherapy And Radiation In Patients With Locally Advanced Pancreatic Cancer

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pancreatic Cancer
  • Drug: fluorouracil
    2700 mg/m5 IV over 24 hr after gemcitabine weeks 1 & 2; Repeat one 3-week cycle starting day 22
  • Drug: gemcitabine hydrochloride
    750 (females) or 900 (males) mg/m5 IV over 30 min (day 2)weeks 1 & 2; Repeat one 3-week cycle starting day 22
  • Drug: leucovorin calcium
    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
  • Drug: oxaliplatin
    48 mg/m5 IV over 2 hr weeks 1, 2, 4, and 5
  • Procedure: adjuvant therapy

    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.

  • Procedure: conventional surgery
    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.
  • Procedure: neoadjuvant therapy
    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.
  • Radiation: radiation therapy
    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).
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
50
Not Provided
December 2013   (final data collection date for primary outcome measure)

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
Both
19 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00089024
035-04, P30CA036727, UNMC-03504
Yes
Jean L. Grem, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
University of Nebraska
National Cancer Institute (NCI)
Study Chair: Jean L. Grem, MD University of Nebraska
University of Nebraska
June 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP