Genistein, Gemcitabine, and Erlotinib in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer

OBJECTIVES:

Primary

• Determine the 6-month survival rate of patients with locally advanced or metastatic pancreatic cancer treated with genistein, gemcitabine hydrochloride, and erlotinib hydrochloride.

Secondary

• Determine the frequency of objective tumor response rate in these patients.
• Determine the time to treatment failure in these patients.
• Determine the effect of baseline expression of pAKT and activation of NF-kappaB on survival of patients treated with this regimen.
• Determine the overall time to disease progression in these patients.
• Estimate the quantitative and qualitative toxicities of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral genistein twice daily on days -7 to 28 in course 1 and on days 1-28 in all other courses. Patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 and oral erlotinib hydrochloride once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed pancreatic adenocarcinoma

• Locally advanced or metastatic disease by radiological evidence
• Must have biopsy material consisting of 10 unstained slides or paraffin-embedded tissue blocks available for correlative studies
• No endocrine tumor or lymphoma of the pancreas
• No history of CNS (central nervous system) metastases

PATIENT CHARACTERISTICS:

• SWOG (Southwest Oncology Group) performance status 0-1
• Life expectancy ≥ 12 weeks
• Platelet count ≥ 100,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Bilirubin < 2.0 mg/dL
• AST (aspartate aminotransferase) and ALT (alanine aminotransferase) < 1.5 times upper limit of normal
• Creatinine < 1.5 mg/dL
• Albumin > 2.5 g/dL
• INR (international normalized ratio) < 1.3 (in the absence of ongoing treatment with warfarin)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No condition that would limit the ability to receive oral medications
• No requirement for a gastrostomy tube for the administration of drugs
• No serious concurrent systemic disorder, that, in the opinion of the investigator, is incompatible with the study
• No active second primary malignancy within the past year except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin
• No allergy to any study drug

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for metastatic disease

• Prior adjuvant chemotherapy allowed provided it was completed at least 6 months ago
• No prior gemcitabine hydrochloride or epidermal growth factor receptor-inhibiting agents
• No other concurrent chemotherapy, immunotherapy, tumor-directed hormonal therapy, or radiotherapy
• No other concurrent investigational agents
• No other concurrent antitumor therapy