Clinical trial NCT00002596: Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors
Official title: RANDOMIZED MULTIINSTITUTIONAL PHASE III TRIAL OF BEP AND HIGH DOSE CHEMOTHERAPY VERSUS BEP ALONE IN PREVIOUSLY UNTREATED PATIENTS WITH POOR RISK GERM CELL TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Testicular Germ Cell Tumor
Keywords: stage II malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
testicular seminoma
testicular embryonal carcinoma
testicular choriocarcinoma
testicular teratoma
testicular yolk sac tumor
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and teratoma with seminoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular embryonal carcinoma and seminoma
testicular yolk sac tumor and teratoma
testicular yolk sac tumor and teratoma with seminoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and seminoma
extragonadal germ cell tumor
childhood teratoma
childhood malignant testicular germ cell tumor
childhood extragonadal germ cell tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
name: SWOG Cancer Research Network
name: Cancer and Leukemia Group B
First posted: 2003-01-27
Enrollment: 270
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not known whether combining chemotherapy with bone marrow or peripheral stem cell transplantation is more effective than combination chemotherapy alone in treating men with germ cell tumors.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bone marrow or peripheral stem cell transplantation in treating men with previously untreated germ cell tumors.

Detailed description: OBJECTIVES:

* Compare the efficacy of bleomycin, etoposide, and cisplatin (BEP) with or without high-dose carboplatin, etoposide, and cyclophosphamide plus autologous bone marrow or peripheral blood stem cell transplantation in male patients with poor- or intermediate-risk germ cell tumors.
* Compare the toxicity of these regimens in these patients.
* Compare prospectively the prognosis in terms of the rate of decline of the serum tumor markers, human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), in patients treated with these regimens.
* Correlate hCG and AFP with complete response and survival in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and risk status (poor vs intermediate). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive bleomycin IV on days 1, 8, and 15 and etoposide (VP-16) IV over 30-60 minutes and cisplatin (CDDP) IV over 30-60 minutes on days 1-5 (BEP). Filgrastim (G-CSF) is administered subcutaneously (SC) on days 7-16 or until blood counts recover. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. G-CSF is discontinued 24 hours before initiating subsequent courses of chemotherapy, and withheld on days of bleomycin administration.
* Arm II: Patients receive 2 courses of BEP and G-CSF as in arm I. Patients who have no marrow involvement with tumor undergo harvest of autologous bone marrow before the first or second course of BEP. Patients who have bone marrow involvement with tumor undergo harvest of G-CSF-mobilized autologous peripheral blood stem cells (PBSC) on days 17-21 of the first and/or second courses of BEP. When blood counts recover, patients receive high-dose intensification comprising carboplatin IV over 1 hour, VP-16 IV over 30-60 minutes, and cyclophosphamide IV over 1 hour on days -5 to -3. Autologous bone marrow or PBSC are reinfused over 15-20 minutes on day 0. G-CSF is administered SC beginning 24 hours after transplantation and continuing until blood counts recover. Beginning 1-3 weeks after hospital discharge for the first transplantation and after recovery from any toxic effects, patients with a Karnofsky performance status of 70-100% receive a second course of high-dose intensification plus a second bone marrow or PBSC transplantation in the absence of disease progression or unacceptable toxicity.

Patients on both arms with brain metastases at presentation undergo radiotherapy and/or surgery concurrently with BEP, if medically indicated.

Patients with normal alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG) tumor marker levels after completion of treatment on arm I or II undergo surgical resection of all residual masses. Patients who have no residual malignant tumor or undergo complete resection of only a mature teratoma receive no further therapy. Patients on arm I who undergo complete resection of residual malignant tumor receive 2 additional courses of VP-16 and CDDP without bleomycin. Patients on arm II who undergo complete resection of residual malignant tumor receive no additional chemotherapy. Patients with an unresectable residual malignant tumor receive additional therapy at the discretion of the treating physician. Patients with residual tumor marker (AFP and hCG) positivity after treatment on arm I or II undergo resection of residual masses if tumor marker values fall to normal by marker half-life.

PROJECTED ACCRUAL: A total of 270 patients (135 per treatment arm) will be accrued for this study within 4.4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven poor-risk, nonseminoma germ cell tumor

  * Must meet 1 of the following 3 conditions:

    * Testis or retroperitoneal primary site without visceral metastasis but with any of the following tumor marker values:

      * Lactic dehydrogenase (LDH) greater than 10 times upper limit of normal (ULN)
      * Human chorionic gonadotropin (hCG) greater than 50,000 IU/L
      * Alpha-fetoprotein (AFP) greater than 10,000 ng/mL
    * Testis or retroperitoneal primary site with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values), including the following:

      * Bone
      * Brain
      * Liver
      * Other nonpulmonary viscera (e.g., skin, spleen)
    * Mediastinal primary site, regardless of presence/absence of visceral metastasis or tumor marker values OR
* Histologically proven intermediate-risk, nonseminoma germ cell tumor

  * Testis or retroperitoneal primary site with no visceral metastasis (except lung), and with any of the following tumor marker values:

    * LDH 3-10 times ULN
    * hCG 5,000-50,000 IU/L
    * AFP 1,000-10,000 ng/mL OR
* Histologically proven intermediate-risk, seminoma germ cell tumor with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values or primary site), including the following:

  * Bone
  * Brain
  * Liver
  * Other nonpulmonary visceral metastasis (e.g., skin, spleen)
* Histologic confirmation may be delayed, at the discretion of the protocol chairman, until after initiation of study therapy for patients with a testicular mass and elevated AFP or hCG if medical circumstances warrant immediate treatment
* Measurable or evaluable disease
* Concurrent registration on protocol MSKCC-89076 (SWOG-9345) for tumor biology studies required

PATIENT CHARACTERISTICS:

Age:

* 12 and over

Sex:

* Male

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 3,000/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* See Disease Characteristics

Renal:

* Creatinine no greater than ULN\* OR
* Creatinine clearance greater than 50 mL/min\* NOTE: \* Abnormal levels due to ureteral obstruction by tumor allowed at the discretion of the protocol chairman

Other:

* HIV negative
* No other concurrent malignancy except nonmelanomatous skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy
* No other concurrent chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 30 days since prior radiotherapy except for brain metastases or documented disease progression
* Recovered from the toxic effects of any prior radiotherapy

Surgery:

* Recovered from the effects of any recent surgery

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Greenbrae
country: United States
facility: Sutter Health Western Division Cancer Research Group
state: California
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital - Orange
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Walnut Creek
country: United States
facility: John Muir Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Veterans Affairs Medical Center - Washington, DC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital Comprehensive Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: West Palm Beach
country: United States
facility: Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center
state: Florida
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Honolulu
country: United States
facility: MBCCOP - Hawaii
state: Hawaii
city: Boise
country: United States
facility: Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Rockford
country: United States
facility: Saint Anthony Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Veterans Affairs Medical Center - Indianapolis (Roudebush)
state: Indiana
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: New Orleans
country: United States
facility: MBCCOP - LSU Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Veterans Affairs Medical Center - Baltimore
state: Maryland
city: Boston
country: United States
facility: Tuft-New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center - University Campus
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Medical Center - St. Joseph
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Health Sciences Center
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Papillion
country: United States
facility: Alegent Health-Midlands Community Hospital
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Veterans Affairs Medical Center - Las Vegas
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Camden
country: United States
facility: Cooper University Hospital
state: New Jersey
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Clinical Cancer Center
state: New York
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Asheville
country: United States
facility: Veterans Affairs Medical Center - Asheville
state: North Carolina
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Fayetteville
country: United States
facility: Cape Fear Valley Health System
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Hospital Cancer Center
state: North Carolina
city: Pinehurst
country: United States
facility: FirstHealth Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Fargo
country: United States
facility: Veterans Affairs Medical Center - Fargo
state: North Dakota
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: CCOP - Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Cancer Institute
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan: The Miriam Hospital
state: Rhode Island
city: Sioux Falls
country: United States
facility: CCOP - Sioux Community Cancer Consortium
state: South Dakota
city: Memphis
country: United States
facility: University of Tennessee Cancer Institute
state: Tennessee
city: Memphis
country: United States
facility: Danville Radiation Therapy Center
state: Tennessee
city: Amarillo
country: United States
facility: Harrington Cancer Center
state: Texas
city: Amarillo
country: United States
facility: Veterans Affairs Medical Center - Amarillo
state: Texas
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Bennington
country: United States
facility: Green Mountain Oncology Group
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Charlottesville
country: United States
facility: Martha Jefferson Hospital
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Norfolk
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Puget Sound Oncology Consortium
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: Green Bay
country: United States
facility: CCOP - St. Vincent Hospital Cancer Center, Green Bay
state: Wisconsin
city: Madison
country: United States
facility: Veterans Affairs Medical Center - Madison
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Medical Research and Education Foundation
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group - Northern Region
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Lima
country: Peru
facility: Instituto de Enfermedades Neoplasicas
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico School of Medicine Medical Sciences Campus
city: San Juan
country: Puerto Rico
facility: San Juan City Hospital
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Robert J. Motzer, MD
role: STUDY_CHAIR
affiliation: Indiana University Melvin and Bren Simon Cancer Center
name: Patrick J. Loehrer, MD
role: STUDY_CHAIR
affiliation: City of Hope Comprehensive Cancer Center
name: Kim A. Margolin, MD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Eric J. Small, MD
role: STUDY_CHAIR
References:
citation: Motzer RJ, Nichols CJ, Margolin KA, Bacik J, Richardson PG, Vogelzang NJ, Bajorin DF, Lara PN Jr, Einhorn L, Mazumdar M, Bosl GJ. Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol. 2007 Jan 20;25(3):247-56. doi: 10.1200/JCO.2005.05.4528.
citation: Bajorin DF, Nichols CR, Margolin KA, et al.: Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): a cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB. [Abstract] J Clin Oncol 24 (Suppl 18): A-4510, 2006.