RATIONALE: Imatinib mesylate 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 imatinib mesylate in treating patients who have progressive, refractory, or recurrent stage II or stage III testicular cancer or stage II or stage III ovarian cancer following cisplatin-based chemotherapy.

Condition	Treatment or Intervention	Phase
ovarian germ cell tumor Testicular Cancer	Drug: imatinib mesylate  Procedure: enzyme inhibitor therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the activity of imatinib mesylate in patients with progressive, refractory, or recurrent pure testicular seminoma or ovarian germ cell dysgerminoma after cisplatin-based chemotherapy.
• Determine the toxicity of this drug in this patient population.
• Determine KIT expression and identify mutations in the c-kit gene in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve a partial response or stable disease with normalization of human chorionic gonadotropin may undergo surgical resection of residual lesions at each tumor status assessment. If residual viable germ cell tumor is present in the resected specimen, patients may resume imatinib mesylate. If no viable germ cell tumor is present in the resected specimen, then no further therapy is administered.

Patients are followed every 3 months for 1 year and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study within 32-38 months.

Ages Eligible for Study:  15 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed pure testicular seminoma or ovarian germ cell dysgerminoma
• Histologic documentation of metastatic/recurrent disease not required
• Alpha-fetoprotein level must be normal, unless abnormal level is explained by other conditions and approved by the study chair
• Clinical stage II or III
• Progressive, refractory, or recurrent disease, meeting at least 1 of the following criteria:
• Measurable progressive disease
• Biopsy-proven residual disease
• Persistently elevated or rising B-human chorionic gonadotropin (HCG) titers, defined as at least 2 values above the upper limit of normal (ULN)
• Cisplatin-refractory disease without option of potentially curative therapy, meeting 1 of the following criteria:
• Failed high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) or autologous bone marrow transplantation (AuBMT)
• Ineligible for or refused PBSCT or AuBMT
• Unlikely to achieve long-term benefit from PBSCT or AuBMT
• Current evidence of metastatic disease
• Unidimensionally measurable target lesions
• At least 20 mm by conventional techniques (e.g., physical examination for clinically palpable lymph nodes and superficial skin lesions or chest x-ray for clearly defined lung lesions surrounded by aerated lung) OR
• At least 10 mm by spiral CT scan or MRI
• If measurable disease is confined to a solitary lesion, then its neoplastic nature must be confirmed by histology
• Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically OR
• Non-measurable/non-target lesions, with HCG at least ULN, including the following:
• Bone lesions
• Pleural or pericardial effusions
• Ascites
• CNS lesions
• Leptomeningeal disease
• Irradiated lesions, unless progression documented after radiotherapy

PATIENT CHARACTERISTICS: Age

• 15 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL (transfusion allowed)

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT no greater than 2.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Other

• No other severe and/or uncontrolled concurrent medical illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics

Chemotherapy

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

Endocrine therapy

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

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• Prior radiotherapy to a symptomatic lesion or one that may produce disability (e.g., unstable femur) allowed
• No concurrent palliative radiotherapy

Surgery

• Not specified

Other

• No concurrent grapefruit juice
• No concurrent warfarin for therapeutic anticoagulation (concurrent mini-dose warfarin [1 mg orally per day] as prophylaxis allowed)

Alabama
      Northeast Alabama Regional Medical Center, Anniston,  Alabama,  36207,  United States
California
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  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, 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,  20307-5000,  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
      Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center, West Palm Beach,  Florida,  33401,  United States
      Memorial Regional Hospital Comprehensive Cancer Center, Hollywood,  Florida,  33021,  United States
Illinois
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States
      Saint Anthony Medical Center, Rockford,  Illinois,  61108,  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
      Hematology Oncology Associates of the Quad Cities, Bettendorf,  Iowa,  52722,  United States
      Holden Comprehensive Cancer Center, Iowa City,  Iowa,  52242-1009,  United States
Kentucky
      Baptist Hospital East - Louisville, Louisville,  Kentucky,  40207,  United States
Maryland
      Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
      Veterans Affairs Medical Center - Baltimore, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Michigan
      Lakeland Medical Center - 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
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  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
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      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
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
New Jersey
      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., Syracuse,  New York,  13217,  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, NY, 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
      State University of New York - Upstate Medical University, 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, Winston Salem,  North Carolina,  27104-4241,  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
      FirstHealth Moore Regional Hospital, Pinehurst,  North Carolina,  28374,  United States
      Lenoir Memorial Hospital Cancer Center, Kinston,  North Carolina,  28503-1678,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      New Hanover Regional Medical Center, Wilmington,  North Carolina,  28402-9025,  United States
      NorthEast Oncology Associates, 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
North Dakota
      Veterans Affairs Medical Center - Fargo, Fargo,  North Dakota,  58102,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Pennsylvania
      Western Pennsylvania Hospital, Pittsburgh,  Pennsylvania,  15224,  United States
Rhode Island
      Lifespan: The Miriam Hospital, Providence,  Rhode Island,  02906,  United States
Texas
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      Veterans Affairs Medical Center - Dallas, Dallas,  Texas,  75216,  United States
Vermont
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  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, Inc., 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
Wisconsin
      Ministry Medical Group - Northern Region, Rhinelander,  Wisconsin,  54501,  United States
Canada, Quebec
      McGill University, Montreal,  Quebec,  H2W 1S6,  Canada
Puerto Rico
      University of Puerto Rico School of Medicine Medical Sciences Campus, San Juan,  00936-5067,  Puerto Rico

Study chairs or principal investigators

Christopher W. Ryan, MD,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000069487; CLB-90105
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  August 5, 2002
ClinicalTrials.gov Identifier:  NCT00042952
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08