RATIONALE: Drugs used in chemotherapy work 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. Flavopiridol may make the tumor cells more sensitive to radiation therapy.

PURPOSE: Phase I trial to study the effectiveness of combining flavopiridol with radiation therapy followed by gemcitabine in treating patients who have locally advanced, unresectable pancreatic cancer.

Condition	Treatment or Intervention	Phase
adenocarcinoma of the pancreas recurrent pancreatic cancer stage II pancreatic cancer stage III pancreatic cancer stage IVA pancreatic cancer	Drug: flavopiridol  Drug: gemcitabine  Procedure: chemotherapy  Procedure: radiation therapy  Procedure: radiosensitization	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of flavopiridol in combination with radiotherapy followed by gemcitabine in patients with locally advanced, unresectable pancreatic cancer.
• Determine the toxicity of this regimen in these patients.
• Determine the pharmacokinetics of flavopiridol in these patients.
• Determine, preliminarily, the therapeutic activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of flavopiridol.

Patients receive flavopiridol IV over 1 hour twice weekly (on days 1 and 4 or days 2 and 5) for 6 weeks. Concurrently, patients undergo radiotherapy once daily 5 days a week for 5.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Four weeks after the completion of radiotherapy, patients are re-evaluated*. Beginning within 4-7 weeks after the completion of radiotherapy, patients receive gemcitabine IV over 30 minutes weekly for 3 weeks. Treatment repeats every 4 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients whose imaging studies suggest potential curative resection are referred for a surgical evaluation before initiating gemcitabine therapy.

Cohorts of 3-6 patients receive escalating doses of flavopiridol 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. Once the MTD is determined, 10 additional patients are treated at the recommended phase II dose.

Patients are followed at 4 weeks and then every 8 weeks thereafter.

PROJECTED ACCRUAL: Approximately 3-46 patients will be accrued for this study within 2 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas
• No non-adenocarcinoma of the pancreas (i.e., islet cell, lymphoma, or sarcoma)
• Locally advanced and unresectable disease defined as the following:
• Obvious encasement of the celiac, hepatic, or superior mesenteric artery
• Encasement of the portal or superior mesenteric vein not amenable to resection
• Extrapancreatic extension with or without regional lymph node involvement
• No distant metastases
• Measurable or evaluable disease
• Primary pancreatic tumor is considered evaluable, not measurable
• A lymph node mass is considered measurable

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

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

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT no greater than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No Crohn's disease or inflammatory bowel disease that would preclude study participation
• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation

Other

• No other uncontrolled concurrent illness that would preclude study participation
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for this disease
• No prior flavopiridol or other cyclin-dependent kinase therapies

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy for this disease

Surgery

• Prior curative surgery with local recurrence allowed

Other

• No other concurrent investigational therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Jeremy S. Kortmansky, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000257662; MSKCC-02057; NCI-5764; NCT00047307
Record last reviewed:  February 2004
Last Updated:  December 6, 2004
Record first received:  October 3, 2002
ClinicalTrials.gov Identifier:  NCT00047307
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08