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

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: gemcitabine hydrochloride; Drug: erlotinib hydrochloride; Dietary supplement: genistein

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Novasoy®, Gemcitabine & Erlotinib; 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	Drug: gemcitabine hydrochloride; Drug: erlotinib hydrochloride; Dietary supplement: genistein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Barbara Ann Karmanos Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Khaldoun Almhanna, MD, Barbara Ann Karmanos Cancer Institute

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): March 1, 2010
• Study Completion (ACTUAL): March 1, 2010

Study Registration Dates

• First Submitted: September 13, 2006
• First Submitted That Met QC Criteria: September 13, 2006
• First Posted (ESTIMATE): September 15, 2006

Study Record Updates

• Last Update Posted (ACTUAL): March 1, 2021
• Last Update Submitted That Met QC Criteria: February 25, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer; stage III pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Estrogens, Non-Steroidal; Estrogens; Protein Kinase Inhibitors; Anticarcinogenic Agents; Phytoestrogens; Gemcitabine; Erlotinib Hydrochloride; Genistein
• Other Study ID Numbers: CDR0000495776; P30CA022453 (U.S. NIH Grant/Contract); WSU-2005-006; WSU-025806MP4F