RATIONALE: PTK787/ZK 222584 may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: Phase II trial to study the effectiveness of PTK787/ZK 222584 in treating patients with unresectable malignant mesothelioma.

Condition	Treatment or Intervention	Phase
advanced malignant mesothelioma epithelial mesothelioma recurrent malignant mesothelioma sarcomatous mesothelioma	Drug: vatalanib  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the efficacy of PTK787/ZK 222584, in terms of 3-month progression-free survival, in patients with malignant mesothelioma.
• Determine the response rate in patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Determine the overall and failure-free survival of patients treated with this drug.
• Correlate pretreatment circulating serum levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor, and VEGF mRNA isoforms with response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral PTK787/ZK 222584 daily. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 1 year, every 4 months for 1 year, and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 9-13 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignant mesothelioma of 1 of the following types:
• Epithelial
• Sarcomatoid
• Mixed
• Not amenable to radiotherapy or curative surgery
• Any site of origin including, but not limited to, the following:
• Pleura
• Peritoneum
• Pericardium
• Tunica vaginalis
• At least one unidimensionally measurable lesion outside of prior irradiation port
• At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• The following are not considered measurable:
• Bone lesions
• Leptomeningeal disease
• Ascites
• Pleural/pericardial effusion
• Lymphangitis cutis/pulmonis
• Abdominal masses that are not confirmed and followed by imaging techniques
• Cystic lesions
• No known brain metastases

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN
• Negative for proteinuria by dipstick OR
• Urinary protein no greater than 500 mg and creatinine clearance at least 50 mL/min

Cardiovascular

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

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception
• No currently active second malignancy except non-melanoma skin cancers (unless therapy is completed and risk of relapse is less than 30%)
• No other concurrent uncontrolled illness
• No ongoing active infections
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior signal transduction inhibitor therapy
• No prior angiogenesis inhibitor therapy

Chemotherapy

• No prior cytotoxic chemotherapy for this malignancy
• No concurrent chemotherapeutic agents
• Prior intrapleural cytotoxic or sclerosing therapy (including bleomycin) allowed

Endocrine therapy

• No concurrent hormonal therapy except steroids for adrenal failure or hormones for non-disease-related conditions (e.g., insulin for diabetes)

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent palliative radiotherapy

Surgery

• See Disease Characteristics
• At least 2 weeks since prior major surgery

Other

• At least 30 days since prior investigational agents
• At least 7 days since prior grapefruit or grapefruit juice
• At least 7 days since prior CYP3A4 inducers
• No prior PTK787/ZK 222584
• No prior tyrosine kinase inhibitor therapy
• No other concurrent investigational agents
• No concurrent isoenzyme inducers or inhibitors of p450
• No concurrent warfarin or similar oral anticoagulants
• Heparin allowed
• No concurrent grapefruit or grapefruit juice
• No concurrent combination antiretroviral therapy for HIV-positive patients

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233-1996,  United States
California
      Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Naval Medical Center - San Diego, San Diego,  California,  92134-3202,  United States
      Rebecca and John Moores UCSD Cancer Center, La Jolla,  California,  92093-0658,  United States
      UCSF Comprehensive Cancer Center, San Francisco,  California,  94115,  United States
      Veterans Affairs Medical Center - San Diego, San Diego,  California,  92161,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Newark,  Delaware,  19713,  United States
District of Columbia
      Lombardi Cancer Center at Georgetown University Medical Center, Washington,  District of Columbia,  20007,  United States
      Veterans Affairs Medical Center - Washington, DC, Washington,  District of Columbia,  20422,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5001,  United States
Florida
      Broward General Medical Center, Fort Lauderdale,  Florida,  33316,  United States
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
      Florida Hospital Cancer Institute, Orlando,  Florida,  32804,  United States
      Memorial Regional Cancer Center at Memorial Regional Hospital, Hollywood,  Florida,  33021,  United States
Illinois
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61615-7828,  United States
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
      West Suburban Center for Cancer Care, River Forest,  Illinois,  60305,  United States
Indiana
      CCOP - Northern Indiana CR Consortium, South Bend,  Indiana,  46601,  United States
      Fort Wayne Medical Oncology and Hematology, Incorporated, Fort Wayne,  Indiana,  46885-5099,  United States
Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Maryland
      Greenebaum Cancer Center at University of Maryland Medical Center, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      UMASS Memorial Cancer Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph, Saint Joseph,  Michigan,  49085,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States
      Ellis Fischel Cancer Center at University of Missouri - Columbia, Columbia,  Missouri,  65203,  United States
      Missouri Baptist Cancer Center, Saint Louis,  Missouri,  63131,  United States
      Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      UNMC Eppley Cancer Center at the University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
      Veterans Affairs Medical Center - Las Vegas, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      New Hampshire Oncology-Hematology, PA - Hooksett, Hooksett,  New Hampshire,  03106,  United States
      Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      Cancer Institute of New Jersey at the Cooper University Hospital, Camden,  New Jersey,  08103,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., East Syracuse,  New York,  13057,  United States
      Elmhurst Hospital Center, Elmhurst,  New York,  11373,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, New York,  New York,  10029,  United States
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Queens Cancer Center of Queens Hospital, Jamaica,  New York,  11432,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      SUNY Upstate Medical University Hospital, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      Cape Fear Valley Health System, Fayetteville,  North Carolina,  28302-2000,  United States
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States
      Comprehensive Cancer Center at Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lenoir Memorial Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill,  North Carolina,  27599-7295,  United States
      NorthEast Oncology Associates - Concord, Concord,  North Carolina,  28025,  United States
      Veterans Affairs Medical Center - Asheville, Asheville,  North Carolina,  28805,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
      Zimmer Cancer Center at New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States
Pennsylvania
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
Tennessee
      University of Tennessee Cancer Institute at Methodist Central Hospital, Memphis,  Tennessee,  38104,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Texas
      Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas, Dallas,  Texas,  75390-8852,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75219,  United States
Vermont
      Vermont Cancer Center at University of Vermont, Burlington,  Vermont,  05401-3498,  United States
Virginia
      Martha Jefferson Hospital, Charlottesville,  Virginia,  22902,  United States
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke, Roanoke,  Virginia,  24014,  United States
      Virginia Oncology Associates - Norfolk, Norfolk,  Virginia,  23502,  United States
West Virginia
      St. Mary's Medical Center, Huntington,  West Virginia,  25701,  United States

Study chairs or principal investigators

Thierry Jahan, MD,  Study Chair,  University of California, San Francisco   

Study ID Numbers:  CDR0000269537; CALGB-30107; NCT00053885
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00053885
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08