Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors

Testicular Germ Cell Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002596
• Other study ID #: SWOG-9442
• Secondary ID: MSKCC-94076CLB-9
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 25, 2013
• Start date: September 1994
• Est. completion date: July 2006

Study information

• Verified date: October 2003
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 270
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 12 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Germ Cell Tumor
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• bleomycin sulfate

• filgrastim

Drug:
• carboplatin

• cisplatin

• cyclophosphamide

• etoposide

Procedure:
• autologous bone marrow transplantation

• bone marrow ablation with stem cell support

• conventional surgery

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Australia	Westmead Hospital	Westmead	New South Wales
Peru	Instituto de Enfermedades Neoplasicas	Lima
Puerto Rico	San Juan City Hospital	San Juan
Puerto Rico	University of Puerto Rico School of Medicine Medical Sciences Campus	San Juan
United States	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico
United States	Harrington Cancer Center	Amarillo	Texas
United States	Veterans Affairs Medical Center - Amarillo	Amarillo	Texas
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Northeast Alabama Regional Medical Center	Anniston	Alabama
United States	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina
United States	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Veterans Affairs Medical Center - Baltimore	Baltimore	Maryland
United States	Green Mountain Oncology Group	Bennington	Vermont
United States	Mountain States Tumor Institute	Boise	Idaho
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Tuft-New England Medical Center	Boston	Massachusetts
United States	Albert Einstein Clinical Cancer Center	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Veterans Affairs Medical Center - Buffalo	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Vermont Cancer Center	Burlington	Vermont
United States	Cooper University Hospital	Camden	New Jersey
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Martha Jefferson Hospital	Charlottesville	Virginia
United States	Louis A. Weiss Memorial Hospital	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri
United States	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri
United States	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio
United States	NorthEast Oncology Associates	Concord	North Carolina
United States	Veterans Affairs Medical Center - Dallas	Dallas	Texas
United States	CCOP - Geisinger Clinic and Medical Center	Danville	Pennsylvania
United States	CCOP - Dayton	Dayton	Ohio
United States	University of Colorado Cancer Center	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Veterans Affairs Medical Center - Durham	Durham	North Carolina
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota
United States	Cape Fear Valley Health System	Fayetteville	North Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Sutter Health Western Division Cancer Research Group	Greenbrae	California
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Memorial Regional Hospital Comprehensive Cancer Center	Hollywood	Florida
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	MBCCOP - Hawaii	Honolulu	Hawaii
United States	St. Mary's Medical Center	Huntington	West Virginia
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Baptist Hospital East - Louisville	Louisville	Kentucky
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	CCOP - North Shore University Hospital	Manhasset	New York
United States	North Shore University Hospital	Manhasset	New York
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Danville Radiation Therapy Center	Memphis	Tennessee
United States	University of Tennessee Cancer Institute	Memphis	Tennessee
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center, NY	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Virginia Oncology Associates - Norfolk	Norfolk	Virginia
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	St. Joseph Hospital - Orange	Orange	California
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Alegent Health-Midlands Community Hospital	Papillion	Nebraska
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Oregon Cancer Institute	Portland	Oregon
United States	Lifespan: The Miriam Hospital	Providence	Rhode Island
United States	Ministry Medical Group - Northern Region	Rhinelander	Wisconsin
United States	MBCCOP - Massey Cancer Center	Richmond	Virginia
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Oncology and Hematology Associates of Southwest Virginia, Inc.	Roanoke	Virginia
United States	James P. Wilmot Cancer Center	Rochester	New York
United States	Saint Anthony Medical Center	Rockford	Illinois
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Lakeland Medical Center - St. Joseph	Saint Joseph	Michigan
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	St. Louis University Health Sciences Center	Saint Louis	Missouri
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Veterans Affairs Medical Center - San Francisco	San Francisco	California
United States	CCOP - Virginia Mason Research Center	Seattle	Washington
United States	Puget Sound Oncology Consortium	Seattle	Washington
United States	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	Stanford University Medical Center	Stanford	California
United States	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Veterans Affairs Medical Center - Syracuse	Syracuse	New York
United States	CCOP - Northwest	Tacoma	Washington
United States	Arizona Cancer Center	Tucson	Arizona
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	John Muir Medical Center	Walnut Creek	California
United States	Lombardi Cancer Center	Washington	District of Columbia
United States	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	Helen and Harry Gray Cancer Institute at Good Samaritan Medical Center	West Palm Beach	Florida
United States	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont
United States	CCOP - Wichita	Wichita	Kansas
United States	New Hanover Regional Medical Center	Wilmington	North Carolina
United States	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (5)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, National Cancer Institute (NCI), Southwest Oncology Group

Countries where clinical trial is conducted

United States,  Australia,  Peru,  Puerto Rico, 

References & Publications (2)

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,

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 hematopoie — View Citation