RATIONALE: Drugs used in chemotherapy use 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. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining chemotherapy and radiation therapy with tipifarnib may be an effective treatment for pancreatic cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of gemcitabine, paclitaxel, and radiation therapy with or without tipifarnib in treating patients who have locally advanced pancreatic cancer.

Condition	Treatment or Intervention	Phase
stage II pancreatic cancer stage III pancreatic cancer adenocarcinoma of the pancreas	Drug: gemcitabine  Drug: paclitaxel  Drug: tipifarnib  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the 1-year survival rate in patients with locally advanced pancreatic cancer treated with paclitaxel, gemcitabine, and radiotherapy with or without tipifarnib.
• Determine the toxicity and loco-regional activity of this chemoradiotherapy regimen in these patients.
• Determine the feasibility and toxicity of prolonged administration of tipifarnib after chemoradiotherapy in these patients.
• Determine whether tipifarnib administered after chemoradiotherapy can increase progression-free and overall survival in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to weight loss in the preceding 6 months (more than 10% vs 10% or less) and tumor dimension (at least 5 cm vs less than 5 cm). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive radiotherapy once daily, 5 days a week, for 5.5 weeks, beginning on day 1. Patients also receive paclitaxel IV over 1 hour and gemcitabine IV over 30 minutes on days 1, 8, 15, 22, 29, and 36.
• Arm II: Patients receive chemoradiotherapy as in arm I. Within 3-8 weeks after completion of chemoradiotherapy, patients without disease progression receive oral tipifarnib twice daily for 21 days. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 154 patients (77 per treatment arm) will be accrued for this study within approximately 20 months.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed unresectable, locally advanced adenocarcinoma of the pancreas
• Residual disease after resection (R1 or R2, microscopic or macroscopic) allowed
• No metastases in major viscera
• No peritoneal seeding or ascites
• Biliary or gastroduodenal obstruction must have drainage before starting study therapy
• Radiographically assessable disease encompassable within a single irradiation field (15 by 15 cm maximum)

PATIENT CHARACTERISTICS: Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,800/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• ALT less than 3 times upper limit of normal
• Bilirubin less than 2.0 mg/dL

Renal:

• Creatinine less than 3.0 mg/dL

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 2 years except non-melanoma skin cancer or carcinoma in situ of the cervix, uterus, or bladder
• No significant infection or other medical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy (including gemcitabine or paclitaxel) for pancreatic cancer
• No other concurrent cytotoxic agents

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy to the planned field
• No other concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent investigational agents

California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States
      Mills-Peninsula Health Services, Burlingame,  California,  94010,  United States
      Providence Saint Joseph Medical Center - Burbank, Burbank,  California,  91505,  United States
      Sutter Health Western Division Cancer Research Group, Greenbrae,  California,  94904,  United States
Colorado
      Memorial Hospital Cancer Center, Colorado Springs,  Colorado,  80909,  United States
Florida
      Baptist Hospital of Miami, Miami,  Florida,  33256-2110,  United States
      University of Florida Health Science Center, Gainesville,  Florida,  32610-0385,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Regional Radiation Oncology Center at Rome, Rome,  Georgia,  30165,  United States
Illinois
      Ingalls Memorial Hospital, Harvey,  Illinois,  60426,  United States
      Richland Memorial Hospital, Olney,  Illinois,  62450,  United States
      Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago,  Illinois,  60611-3013,  United States
Indiana
      Union Hospital, Terre Haute,  Indiana,  47804,  United States
      Veterans Affairs Medical Center - Indianapolis (Roudebush), Indianapolis,  Indiana,  46202,  United States
Louisiana
      Baton Rouge General Medical Center, Baton Rouge,  Louisiana,  70821-2511,  United States
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      Mary Bird Perkins Cancer Center, Baton Rouge,  Louisiana,  70809,  United States
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States
      Medical Center of Louisiana at New Orleans, New Orleans,  Louisiana,  70140-1015,  United States
Maryland
      Greater Baltimore Medical Center and Cancer Center, Baltimore,  Maryland,  21204,  United States
Massachusetts
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Cape Cod Hospital, Hyannis,  Massachusetts,  02601,  United States
Michigan
      Genesys Regional Medical Center, Grand Blanc,  Michigan,  48439-8066,  United States
      Saint Joseph Mercy Hospital, Ypsilanti,  Michigan,  48197,  United States
      Seton Cancer Institute - West Branch, West Branch,  Michigan,  48661,  United States
      St. John Macomb Hospital, Warren,  Michigan,  48093-3494,  United States
      St. Joseph Mercy Hospital, Pontiac,  Michigan,  48341-2985,  United States
      West Michigan Cancer Center, Kalamazoo,  Michigan,  49007,  United States
      William Beaumont Hospital, Royal Oak,  Michigan,  48073,  United States
Minnesota
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States
Nebraska
      Methodist Hospital Cancer Center - Omaha, Omaha,  Nebraska,  68114,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Jersey
      Atlantic City Medical Center, Pomona,  New Jersey,  08240,  United States
      Community Medical Center, Toms River,  New Jersey,  08755,  United States
      Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital, Mount Holly,  New Jersey,  08060,  United States
      Monmouth Medical Center, Long Branch,  New Jersey,  07740-6395,  United States
      Newark Beth Israel Medical Center, Newark,  New Jersey,  07112,  United States
North Carolina
      Margaret Pardee Memorial Hospital, Hendersonville,  North Carolina,  28791,  United States
      Wayne Memorial Hospital, Inc., Goldsboro,  North Carolina,  27533,  United States
Ohio
      Akron City Hospital, Akron,  Ohio,  44304,  United States
      Akron General Medical Center, Akron,  Ohio,  44302,  United States
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States
      Miami Valley Hospital, Dayton,  Ohio,  45409,  United States
Oklahoma
      Natalie Warren Bryant Cancer Center, Tulsa,  Oklahoma,  74136,  United States
      St. John Health System, Tulsa,  Oklahoma,  74104,  United States
Oregon
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212,  United States
      Bryn Mawr Hospital, Bryn Mawr,  Pennsylvania,  19010,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Delaware County Memorial Hospital, Drexel Hill,  Pennsylvania,  19026,  United States
      Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia,  Pennsylvania,  19107-5541,  United States
      Lankenau Cancer Center, Wynnewood,  Pennsylvania,  19096,  United States
      Lehigh Valley Hospital, Allentown,  Pennsylvania,  18105,  United States
      Mercy Fitzgerald Hospital, Darby,  Pennsylvania,  19023,  United States
      Paoli Memorial Hospital, Paoli,  Pennsylvania,  19301-1792,  United States
      Reading Hospital and Medical Center, Reading,  Pennsylvania,  19612-6052,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      Greenville Hospital System, Greenville,  South Carolina,  29605,  United States
Texas
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States
Utah
      Cottonwood Hospital Medical Center, Murray,  Utah,  84107,  United States
      Dixie Regional Medical Center, Saint George,  Utah,  84770,  United States
      Latter Day Saints Hospital, Salt Lake City,  Utah,  84143,  United States
      McKay-Dee Hospital Center, Ogden,  Utah,  84403,  United States
      University of Utah Health Sciences Center, Salt Lake City,  Utah,  84132,  United States
      Utah Valley Regional Medical Center - Provo, Provo,  Utah,  84604,  United States
Virginia
      Danville Regional Medical Center, Danville,  Virginia,  24541,  United States
Washington
      Deaconess Medical Center, Spokane,  Washington,  99204,  United States
      University of Washington Medical Center, Seattle,  Washington,  98195-6043,  United States
      Yakima Valley Memorial Hospital, Yakima,  Washington,  98902,  United States
Wisconsin
      All Saints Cancer Center, Racine,  Wisconsin,  53405,  United States
      CCOP - St. Vincent Hospital Cancer Center, Green Bay, Green Bay,  Wisconsin,  54301,  United States
      Community Memorial Hospital, Menomonee Falls,  Wisconsin,  53051,  United States
      St. Luke's Medical Center, Milwaukee,  Wisconsin,  53215,  United States
Canada, New Brunswick
      Saint John Regional Hospital, Saint John,  New Brunswick,  E2L 4L2,  Canada

Study chairs or principal investigators

Tyvin Andrew Rich, MD,  Study Chair,  University of Virginia, Health Sciences Center Cancer Center   

Study ID Numbers:  CDR0000068986; RTOG-PA-0020; RTOG-DEV-1003
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  November 9, 2001
ClinicalTrials.gov Identifier:  NCT00026104
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08