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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase II Trial of Novasoy®, Gemcitabine, and Erlotinib in Locally Advanced or Metastatic Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Dietary Supplement: genistein
* Drug: erlotinib hydrochloride
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Novasoy®, Gemcitabine & Erlotinib<br>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 | Dietary Supplement: genistein<br> <br> Drug: erlotinib hydrochloride<br> <br> Drug: gemcitabine hydrochloride<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Alive |  | at 6 months | 
| Median Overall Survival Estimate |  | up to 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Objective Response Rate (Complete and Partial Response) | Imaging tests (CT scan, CXR [Chest X-Ray], MRI or imaging studies as clinically indicated | Every 8 weeks | 
| Response Duration | Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. Partial response is defined as greater than or equal to 30% reduction in the sum of the longest diameteres of target lesions, taking as reference the baseline sum of the longest diameters. | Every 8 weeks | 
| Time to Treatment Failure | Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. | Every 8 weeks | 
| Time to Progression | Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated). Progressive disesase is defined as a greater than 20% increase in the sum of the longest diameter of target lesions taking as reference the smalles sum of the longest diameter recorded since the treatment started or the appearance of new lesions. | Every 8 weeks | 
| Grade 3 or Higher Toxicity Evaluation | Toxicity evaluation using NCI-CTC (Common Terminology Criteria) v.3 criteria; CBC (complete blood count) with differential white cell and platelet counts; Serum sodium, potassium, chloride, bicarbonate, AST, ALT, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, and albumin; Serum CA 19-9 | First day of each cycle | 
| pAKT (Pichia Anomala Killer Toxin) and NF (Nuclear Factor)-kappaB Activation | Tumor tissue collected from paraffin | At start of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the pancreas, stage III pancreatic cancer, stage IV pancreatic cancer, recurrent pancreatic cancer