RATIONALE: Drugs used in chemotherapy such as gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Pemetrexed disodium may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining gemcitabine with pemetrexed disodium may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining gemcitabine with pemetrexed disodium in treating patients who have unresectable or metastatic biliary tract or gallbladder cancer.

Condition	Treatment or Intervention	Phase
advanced adult primary liver cancer unresectable gallbladder cancer unresectable extrahepatic bile duct cancer adult primary cholangiocellular carcinoma	Drug: gemcitabine  Drug: pemetrexed disodium  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of gemcitabine when administered with pemetrexed disodium in patients with unresectable or metastatic biliary tract or gallbladder cancer.
• Determine the 6-month survival rate of patients treated with this regimen.
• Determine the best objective tumor response rate and duration of best objective tumor response in patients treated with this regimen.
• Determine the time to progression and overall survival of patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Determine the individual patient variation in toxicity of and/or response to this regimen due to genetic differences in proteins involved in drug response in these patients.

OUTLINE: This is a multicenter phase I dose-escalation study of gemcitabine followed by a phase II study.

• Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
• Phase II: Patients receive pemetrexed disodium as in phase I and gemcitabine at the recommended phase II dose. Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 85 patients (20 for phase I and 65 for phase II) will be accrued for this study within 2.5 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• One of the following histologically or cytologically confirmed cancers not amenable to treatment with combined chemotherapy and radiotherapy:
• Biliary tract (intrahepatic, extrahepatic, or ampulla of Vater) carcinoma
• Gallbladder carcinoma
• Unresectable or metastatic disease
• No CNS metastases
• Prior brain metastases treated with surgery or radiosurgery allowed provided treatment was completed at least 4 weeks ago and there is no evidence of CNS progression
• No clinically significant pericardial or pleural effusion or ascites unless able to be drained before study entry

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 3 times upper limit of normal (ULN)
• AST no greater than 5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 45 mL/min

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
• Able to tolerate folic acid, corticosteroids, or cyanocobalamin supplements

PRIOR CONCURRENT THERAPY: Biologic therapy

• More than 4 weeks since prior biologic or immunologic therapy
• No prior biologic or immunologic therapy for metastatic disease
• No concurrent immunotherapy
• No concurrent colony-stimulating factors during course 1

Chemotherapy

• No prior chemotherapy for metastatic disease
• No prior gemcitabine
• Prior chemoembolization allowed provided the following are true:
• At least 4 weeks since prior chemoembolization
• Evidence of new tumor growth since therapy
• At least 6 months since prior chemotherapy used as a radiosensitizer (in adjuvant setting or for locally advanced disease)
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Prior radiofrequency ablation allowed provided the following are true:
• At least 4 weeks since prior radiofrequency ablation
• Evidence of new tumor growth since therapy
• No prior radiotherapy to 25% or more of the bone marrow
• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• Prior embolization allowed provided the following are true:
• At least 4 weeks since prior embolization
• Evidence of new tumor growth since therapy
• No prior pemetrexed disodium
• No aspirin or nonsteroidal anti-inflammatory drugs for at least 2 days (5 days for long-acting agents [e.g., piroxicam]) before, during, and for at least 2 days after administration of pemetrexed disodium
• No concurrent cyclo-oxygenase-2 inhibitors

Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States
Florida
      Mayo Clinic - Jacksonville, Jacksonville,  Florida,  32224,  United States
Illinois
      BroMenn Regional Medical Center, Normal,  Illinois,  61761,  United States
      Cancer Treatment Center at Pekin Hospital, Pekin,  Illinois,  61554,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States
      Community Cancer Center, Normal,  Illinois,  61761,  United States
      Community Hospital of Ottawa, Ottawa,  Illinois,  61350,  United States
      Eureka Hospital, Eureka,  Illinois,  61530,  United States
      Galesburg Clinic, Galesburg,  Illinois,  61401,  United States
      Galesburg Cottage Hospital, Galesburg,  Illinois,  61401,  United States
      Graham Hospital, Canton,  Illinois,  61520,  United States
      Hopedale Medical Complex, Hopedale,  Illinois,  61747,  United States
      Illinois Valley Community Hospital, Peru,  Illinois,  61354,  United States
      Intercommunity Cancer Center, Lisle,  Illinois,  60532,  United States
      Kewanee Hospital, Kewanee,  Illinois,  61443,  United States
      Mason District Hospital, Havana,  Illinois,  62644,  United States
      McDonough District Hospital, Macomb,  Illinois,  61455,  United States
      Memorial Hospital, Carthage,  Illinois,  62321,  United States
      Methodist Medical Center of Illinois, Peoria,  Illinois,  61636,  United States
      Oncology Hematology Associates of Central Illinois - Ottawa, Ottawa,  Illinois,  61350,  United States
      Oncology/Hematology Associates of Central Illinois, P.C., Peoria,  Illinois,  61615-7828,  United States
      OSF St. Francis Medical Center, Peoria,  Illinois,  61637,  United States
      Perry Memorial Hospital, Princeton,  Illinois,  61356,  United States
      Proctor Hospital, Peoria,  Illinois,  61614,  United States
      Saint Joseph Hospital, Chicago,  Illinois,  60657,  United States
      Sarah D. Culbertson Memorial Hospital, Rushville,  Illinois,  62681,  United States
      St. Margaret's Hospital, Spring Valley,  Illinois,  61362,  United States
      Valley Cancer Center, Spring Valley,  Illinois,  61362,  United States
Iowa
      CCOP - Cedar Rapids Oncology Project, Cedar Rapids,  Iowa,  52403-1206,  United States
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Des Moines General Hospital, Des Moines,  Iowa,  50309,  United States
      Iowa Clinic - Iowa Methodist Campus, Des Moines,  Iowa,  50309,  United States
      Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      Medical Oncology and Hematology Associates at John Stoddard Cancer Center, Des Moines,  Iowa,  50309,  United States
      Medical Oncology and Hematology Associates at Mercy Cancer Center, Des Moines,  Iowa,  50314,  United States
      Mercy Cancer Center at Mercy Medical Center - Des Moines, Des Moines,  Iowa,  50314,  United States
      Mercy Hospital, Iowa City,  Iowa,  52245,  United States
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States
      St. Luke's Hospital, Cedar Rapids,  Iowa,  52406,  United States
      St. Luke's Regional Medical Center, Sioux City,  Iowa,  51104,  United States
Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States
Pennsylvania
      CCOP - Geisinger Clinic and Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      Geisinger Medical Group, State College,  Pennsylvania,  16801,  United States
      Geisinger Wyoming Valley Medical Center, Wilkes Barre,  Pennsylvania,  18711,  United States
South Dakota
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States

Study chairs or principal investigators

Steven R. Alberts, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000298862; NCCTG-N9943; NCT00059865
Record last reviewed:  March 2005
Last Updated:  March 3, 2005
Record first received:  May 6, 2003
ClinicalTrials.gov Identifier:  NCT00059865
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08