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

Barbara Ann Karmanos Cancer Institute

Status and phase: Completed; Phase 2

Conditions: Pancreatic Cancer

Treatments: Dietary Supplement: genistein; Drug: gemcitabine hydrochloride; Drug: erlotinib hydrochloride

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00376948

WSU-2005-006

P30CA022453 (U.S. NIH Grant/Contract)

CDR0000495776

WSU-025806MP4F

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Genistein may help gemcitabine and erlotinib kill more tumor cells by making tumor cells more sensitive to the drugs.

PURPOSE: This phase II trial is studying how well giving genistein together with gemcitabine and erlotinib works in treating patients with locally advanced or metastatic pancreatic cancer.

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 21 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Novasoy®, Gemcitabine & Erlotinib

Experimental group

Description:

Novasoy® 396 mg (177 mg of Isoflavones) twice-daily starting daay -7 until day 28; Gemcitabine 1000 mg/m2 days 1, 8, \& 15; Erlotinib 150 mg day 1 until day 28

Treatment:

Dietary Supplement: genistein

Drug: gemcitabine hydrochloride

Drug: erlotinib hydrochloride