Genistein, Gemcitabine, and Erlotinib in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pancreatic Cancer	Dietary Supplement: genistein Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Trial of Novasoy®, Gemcitabine, and Erlotinib in Locally Advanced or Metastatic Pancreatic Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Genistein Gemcitabine Gemcitabine hydrochloride Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:

Survival [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Every 6 months after off study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall objective response rate (complete and partial response) [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated
Response duration, time to treatment failure, and time to progression [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
Imaging tests (CT scan, CXR, MRI or imaging studies as clinically indicated
Toxicity [ Time Frame: First day of each cycle ] [ Designated as safety issue: Yes ]
Toxicity evaluation using NCI-CTC v.3 criteria; CBC 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
pAKT and NF-kappaB activation [ Time Frame: At start of study ] [ Designated as safety issue: No ]
Tumor tissue collected from paraffin

Enrollment:	20
Study Start Date:	May 2005
Study Completion Date:	March 2010
Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	Dietary Supplement: genistein Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride

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.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 metastases

PATIENT CHARACTERISTICS:

SWOG 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 and ALT < 1.5 times upper limit of normal
Creatinine < 1.5 mg/dL
Albumin > 2.5 g/dL
INR < 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00376948

Locations

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

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Khaldoun Almhanna, MD	Barbara Ann Karmanos Cancer Institute
Principal Investigator:	Fazlul H. Sarkar, PhD	Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:	NCT00376948 History of Changes
Other Study ID Numbers:	CDR0000495776, P30CA022453, WSU-2005-006, WSU-025806MP4F
Study First Received:	September 13, 2006
Last Updated:	May 1, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Barbara Ann Karmanos Cancer Institute:

adenocarcinoma of the pancreas
stage III pancreatic cancer
stage IV pancreatic cancer
recurrent pancreatic cancer

Additional relevant MeSH terms:

Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Genistein
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Anticarcinogenic Agents

ClinicalTrials.gov processed this record on June 18, 2013