Phase I Study of Erlotinib in Patients With Solid Tumors and Hepatic or Renal Dysfunction

OBJECTIVES

I. Determine the maximum tolerated dose of erlotinib in patients with solid tumors and hepatic or renal dysfunction.

II. Determine the pharmacokinetics of this drug in these patients.

ENTRY CRITERIA

--Disease Characteristics--

• Histologically confirmed solid tumor, including gliomas and epithelial malignancies, e.g:
  Non-small cell lung
  Mesothelioma
  Breast
  Head and neck
  Esophageal
  Pancreatic
  Bladder
  Prostate
  Ovarian
  Colorectal carcinoma
  Cervical carcinoma
  Hepatocellular carcinoma
  
• Metastic or unresectable

• Standard curative or palliative therapy does not exist or is no longer effective

• Epidermal growth factor receptor (EGFR) positive

• Hepatic or renal dysfunction with one of the following:
  Direct bilirubin 1.0-7.0 mg/dL and any AST
  AST at least 3 times upper limits of normal
  Creatinine 1.6-5.0 mg/dL

• Brain metastases allowed provided patient is asymptomatic, previously treated, has stable disease for at least 2 months, and is not currently receiving steroid therapy

• Hormone receptor status:
  Not specified

--Prior/Concurrent Therapy--

Biologic therapy

• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for melphalan or mitomycin)
• No prior nitrosoureas

Endocrine therapy

• See Disease Charactertics
• No concurrent steroids

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• At least 4 weeks since prior major surgery
• No prior surgical procedures affecting absorption

Other

• No prior EGFR-targeting therapies, including ZD 1839 or Imclone C-225
• At least 3 months since prior suramin
• At least 7 days since prior CYP3A4 inducers
• No concurrent CYP3A4 inducers, substrates, or inhibitors
• No concurrent medications known to affect hepatic or renal function,including antiseizure medication, or nonsteroidal anti-inflammatory agents
• No concurrent combination anti-retroviral therapy for HIV-positive patients

--Patient Characteristics--

Age: 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance Status

• ECOG 0-2

Life Expectency

• Not specified

Hematopoietic

• Granulocyte cound at least 1,500/mm3
• Platelet count at least 100.00/mm3

Hepatic

• See Disease Characteristics
• No evidence of biliary obstruction

Renal

• See Disease Characteristics
• No evidence of renal obstruction

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• No gastrointestinal tract disease that would preclude ability to take oral
  medications
• No requirement for IV alimentation
• No active peptic ulcer diseas

Ophthalmic

• No prior corneal abnormalities (e.g., dry eye syndrome or Sjogren'ssyndrome)
• No prior congenital abnormality (e.g., Fuch's dystrophy)
• No prior abnormal slit-lamp exam using a vital dye (e.g., fluorescein or Bengal-Rose)
• No abnormal corneal sensitivity test (e.g., Schirmer test or similar tear production test)

Other

• No other uncontrolled concurrent illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study
• Not pregnant or nursing
• Fertile patients must use effective contraception

Projected Accrual

A maximum of 75 patients will be accrued for this study.

OUTLINE

This is a dose-escalation, multicenter study. Patients are stratified according to hepatic or renal dysfunction (albumin less than 2.5 g/dL, direct bilirubin less than 1.0 mg/dL, any AST, and creatinine normal vs direct bilirubin 1.0-7.0 mg/dL, any AST, and creatinine normal vs creatinine 2.5-5.0 mg/dL, albumin 2.5 g/dL or greater, AST less than 3 times upper limit of normal, and direct bilirubin less than 1.0 mg/dL).

Patients receive oral erlotinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 6 evaluable patients are treated at that dose.

Disclaimer

The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.

The study sites listed for this clinical trial are potential study sites; however, not all sites may be participating.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Antonius Miller, MD, Protocol chair Ph: 336-713-4392

Trial Sites and Contacts

U.S.A.

Alabama
Anniston
Northeast Alabama Regional Medical Center
Thomas Twele, MD
Ph: 256-236-2549

California
San Diego
Naval Medical Center - San Diego
Charles Kuzma, MD
Ph: 619-532-7303

Veterans Affairs Medical Center - San Diego
Saeeda Kirmani, MD
Ph: 619-552-8585 ext. 3356
Email: skirmani@ucsd.edu

San Francisco
UCSF Comprehensive Cancer Center
Alan Venook, MD
Ph: 800-888-8664

District of Columbia
Washington
Lombardi Cancer Center at Georgetown University Medical Center
Edward Gelmann, MD
Ph: 202-444-7303
Email: gelmanne@georgetown.edu

Veterans Affairs Medical Center - Washington, DC
Steven Krasnow, MD
Ph: 202-745-8178
Email: krasnow.steven@washington.va.gov

Florida
Hollywood
Memorial Regional Cancer Center at Memorial Regional Hospital
Atif Hussein, MD
Ph: 954-986-6363

Illinois
Chicago
Louis A. Weiss Memorial Hospital
Keith Shulman, MD
Ph: 773-564-5022
Email: KShulman@weisshospital.org

University of Chicago Cancer Research Center
Karen Wendling
Ph: 773-834-7424
888-824-0200

Peoria
CCOP - Illinois Oncology Research Association
John Kugler, MD
Ph: 309-243-3605
800-793-2262

River Forest
West Suburban Center for Cancer Care
John Showel, MD
Ph: 708-763-2700
Email: doc.shoj@wsmc.org

Indiana
Fort Wayne
Fort Wayne Medical Oncology and Hematology, Incorporated
Sreenivasa Nattam, MD
Ph: 260-484-8830
800-852-2333
Email: ledgar@fwmoh.com

Iowa
Iowa City
Holden Comprehensive Cancer Center at University of Iowa
Gerald Clamon, MD
Ph: 319-356-8110

Kentucky
Louisville
Baptist Hospital East - Louisville
Daniel Scullin, MD
Ph: 502-897-1166

Maryland
Baltimore
Greenebaum Cancer Center at University of Maryland Medical Center
Martin Edelman, MD
Ph: 410-328-2703
Email: medelman@umm.edu

Michigan
Saint Joseph
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
Cynthia Bender, BA, CRA
Ph: 269-985-4516
Email: cbender@lakelandregional.org

Nevada
Las Vegas
Veterans Affairs Medical Center - Las Vegas
Chitha Hulugalle, MD
Ph: 702-696-3000

New Hampshire
Hooksett
New Hampshire Oncology-Hematology, PA - Hooksett
Douglas Weckstein, MD
Ph: 603-622-6484
Email: d.weckstein@nhoh.com

Lebanon
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lionel Lewis, MD
Ph: 603-650-8685
800-639-6918

Marc Stuart Ernstoff, MD
Ph: 603-650-5534
800-639-6918
Email: Marc.S.Ernstoff@Hitchcock.org

New Jersey
Camden
Cancer Institute of New Jersey at the Cooper University Hospital
Edison Catalano, MD
Ph: 856-342-2506
800-8-COOPER

New York
Buffalo
Roswell Park Cancer Institute
Ellis Levine, MD
Ph: 716-845-8547
800-685-6825

Elmhurst
Elmhurst Hospital Center
Vladimir Benisovich, MD
Ph: 718-334-3723
Email: beniso@aol.com

Jamaica
Queens Cancer Center of Queens Hospital
Hans Grunwald, MD
Ph: 718-883-4118
Email: hans.grunwald@mssm.edu

Manhasset
North Shore University Hospital
Daniel Budman, MD
Ph: 516-562-8958

New York
Memorial Sloan-Kettering Cancer Center
Clifford Hudis, MD
Ph: 212-639-6483

North Carolina
Asheville
Veterans Affairs Medical Center - Asheville
John Lucke, MD
Ph: 828-299-2540

Concord
NorthEast Oncology Associates - Concord
James Wall, MD
Ph: 704-783-1370
Email: jwall@northeastmedical.org

Fayetteville
Cape Fear Valley Health System
Kamal Bakri, MD
Ph: 910-609-6910

Kinston
Lenoir Memorial Cancer Center
Peter Watson, MD
Ph: 919-559-2200 Ext. 201

Pinehurst
Comprehensive Cancer Center at Moore Regional Hospital
Ellen Willard, MD
Ph: 910-295-9205

Wilmington
Zimmer Cancer Center at New Hanover Regional Medical Center
Cyrus Kotwall, MD
Ph: 910-763-4630
877-228-8135

Winston-Salem
Comprehensive Cancer Center at Wake Forest University
David Duane Hurd, MD
Ph: 336-716-2088
Email: dhurd@wfubmc.edu

Ohio
Columbus
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State
University
Clara Bloomfield, MD
Ph: 614-293-7518
800-293-5066
Email: bloomfield-1@medctr.osu.edu

Oklahoma
Oklahoma City
Oklahoma University Medical Center
Howard Ozer, MD, PhD
Ph: 405-271-4022

Virginia
Charlottesville
Martha Jefferson Hospital
Stefan Gorsch, MD
Ph: 434-982-8410

Norfolk
Virginia Oncology Associates - Norfolk
Paul Conkling, MD
Ph: 757-466-8683

Roanoke
Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
Paul Richards, MD
Ph: 540-982-0237
Email: paul.richards@usoncology.com

West Virginia
Huntington
St. Mary's Medical Center
Gerrit Kimmey, MD
Ph: 304-528-4645

Wisconsin

Rhinelander
Ministry Medical Group at Saint Mary's Hospital
Dhimant Patel, MD
Ph: 715-361-4714
800-866-8673
Email: dpatel@shsmh.org

*** POSTED ON NOVEMBER 11, 2002 ***
*** RE-POSTED JANUARY 18, 2005 ***