RATIONALE: Drugs used in chemotherapy such as gemcitabine and irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining gemcitabine with irinotecan in treating patients who have cancer of unknown primary origin.

Condition	Treatment or Intervention	Phase
adenocarcinoma of unknown primary newly diagnosed carcinoma of unknown primary squamous cell carcinoma of unknown primary undifferentiated carcinoma of unknown primary	Drug: gemcitabine  Drug: irinotecan  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the response rate in patients with carcinoma of unknown primary when treated with gemcitabine and irinotecan.
• Determine the adverse event profile and tolerability of this regimen, based on the presence or absence of the UGT1A1*28 polymorphism, in these patients. (Cohort I) (temporarily closed to accrual as of 2/8/05)
• Determine the adverse event profile and tolerability of this regimen, when dosed according to the relationship between toxicity and UGT1A1 genotype found in cohort I, in these patients. (Cohort II)

Secondary

• Determine the time to progression and overall survival of patients treated with this regimen.
• Correlate patterns of immunohistochemical staining with response in patients treated with this regimen.
• Correlate variation in multiple different genes, whose protein products are involved in the uptake, metabolism, and distribution of these drugs, with clinical outcomes, in terms of response and toxicity, in these patients.

OUTLINE:

• Cohort I (temporarily closed to accrual as of 2/8/05): Patients receive gemcitabine IV over 30 minutes and irinotecan IV over 90 minutes on days 1, 8, 15, and 22. Irinotecan dose may be escalated or de-escalated after course 1 depending on toxicity. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
• Cohort II: Patients receive treatment as in cohort I at a dose determined by the relationship of the UGT1A1*28 polymorphism and toxicity in cohort I. Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 17-54 patients (6 patients with the UGT1A1*28 polymorphism and 6 patients without the UGT1A1*28 polymorphism for cohort I [temporarily closed to accrual as of 2/8/05] and 5-42 for cohort II) will be accrued for this study within approximately 18 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of undetermined origin, with any of the following light microscopic diagnoses:
• Adenocarcinoma
• Poorly differentiated non-small cell carcinoma
• Poorly differentiated squamous cell carcinoma
• Primary site not revealed by the following diagnostic tests:
• Complete history and physical
• Complete blood count and chemistries
• Chest x-ray and/or CT scan
• Abdominal CT scan
• Directed evaluation of symptomatic areas
• Mammogram in women
• Colonoscopy in patients with liver metastases to exclude a colon primary
• Measurable disease
• Must have undergone UGT1A1 genotyping
• Patients with any of the following conditions are not eligible:
• Neuroendocrine tumors
• Women with axillary node involvement only
• Women with adenocarcinoma of the peritoneum
• Carcinoma involving only 1 site, with resectable tumor at that site
• Squamous cell carcinoma limited to cervical, supraclavicular, or inguinal lymph nodes
• Men with poorly differentiated mediastinal or retroperitoneal tumor with stains suggestive of germ cell origin or serum tumor markers (AFP/HCG)
• Men with prominent blastic bony metastases or markedly elevated prostate-specific antigen, suggesting prostate origin
• No brain or meningeal involvement

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

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

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 3 times ULN
• AST no greater than 3 times ULN (5 times ULN if liver metastases are present)
• No known Gilbert's syndrome

Renal

• Creatinine no greater than 2.0 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other invasive malignancy within the past 5 years
• No other severe concurrent disease that would make the patient inappropriate for the study in the judgment of the investigator
• No uncontrolled infection

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent biologic agents
• No concurrent filgrastim (G-CSF)

Chemotherapy

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to more than 25% of the bone marrow
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior major surgery

Arizona
      CCOP - Mayo Clinic Scottsdale Oncology Program, Scottsdale,  Arizona,  85259-5404,  United States; Recruiting
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States; Recruiting
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States; Recruiting
Iowa
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States; Recruiting
      Siouxland Hematology-Oncology, Sioux City,  Iowa,  51101-1733,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States; Recruiting
      CCOP - Metro-Minnesota, Saint Louis Park,  Minnesota,  55416,  United States; Recruiting
      Mayo Clinic - Jacksonville, Rochester,  Minnesota,  55905,  United States; Recruiting
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States; Recruiting
      Medcenter One Health System, Bismarck,  North Dakota,  58501-5505,  United States; Recruiting
Ohio
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
South Carolina
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57104,  United States; Recruiting
      Rapid City Regional Hospital, Rapid City,  South Dakota,  57709,  United States; Recruiting

Study chairs or principal investigators

Mathew P. Goetz, MD,  Study Chair,  Mayo Clinic Cancer Center   
Preston D. Steen, MD,  Meritcare Roger Maris Cancer Center   
Charles Erlichman, MD,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000318830; NCCTG-N004E; NCT00066781
Record last reviewed:  February 2005
Last Updated:  April 4, 2005
Record first received:  August 6, 2003
ClinicalTrials.gov Identifier:  NCT00066781
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08