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.

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 chemotherapy and radiotherapy, patients receive gemcitabine alone or in combination with another cytotoxic agent or gemcitabine combined with a targeted drug (e.g., erlotinib or bevacizumab) at the discretion of the oncologist.

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.

• Drug: alvocidib
• Drug: gemcitabine hydrochloride
• Radiation: radiation therapy

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 except gemcitabine hydrochloride-based therapy for which no radiologic evidence of distant metastatic disease exists
• 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