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

Barbara Ann Karmanos Cancer Institute20 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 21 YearsMax age: 120 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Patients Alive

Time frame: at 6 months

Median Overall Survival Estimate

Time frame: up to 17 months

Secondary Outcomes

Overall Objective Response Rate (Complete and Partial Response)

Imaging tests (CT scan, CXR \[Chest X-Ray\], MRI or imaging studies as clinically indicated

Time frame: 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.

Time frame: Every 8 weeks

Time to Treatment Failure

Time frame: Every 8 weeks

Time to Progression

Time frame: 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

Time frame: First day of each cycle

pAKT (Pichia Anomala Killer Toxin) and NF (Nuclear Factor)-kappaB Activation

Tumor tissue collected from paraffin

Time frame: At start of study

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes