Clinical trial NCT00072215: Cisplatin and Ifosfamide Combined With Either Paclitaxel or Vinblastine in Treating Men With Progressive or Recurrent Metastatic Germ Cell Tumors
Official title: A Randomized Phase III Study of Paclitaxel, Ifosfamide and Cisplatin Versus Vinblastine, Ifosfamide and Cisplatin as Second-Line Therapy for Patients With Relapsed/Resistant Germ Cell Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Extragonadal Germ Cell Tumor
Testicular Germ Cell Tumor
Keywords: recurrent malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and seminoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma
testicular embryonal carcinoma and seminoma
testicular embryonal carcinoma and teratoma with seminoma
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma
testicular seminoma
testicular yolk sac tumor and teratoma with seminoma
testicular yolk sac tumor and teratoma
testicular yolk sac tumor
recurrent extragonadal non-seminomatous germ cell tumor
recurrent extragonadal seminoma
stage IV extragonadal non-seminomatous germ cell tumor
stage IV extragonadal seminoma
testicular immature teratoma
testicular mature teratoma
recurrent extragonadal germ cell tumor
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-11-06
Enrollment: 1
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as ifosfamide, cisplatin, paclitaxel, and vinblastine, work in different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether ifosfamide and cisplatin are more effective when combined with paclitaxel or vinblastine in treating germ cell tumors.

PURPOSE: This randomized phase III trial is studying paclitaxel, ifosfamide, and cisplatin to see how well they work compared to vinblastine, ifosfamide, and cisplatin in treating men with progressive or recurrent metastatic germ cell tumors.

Detailed description: OBJECTIVES:

Primary

* Compare the overall survival of men with progressive or recurrent metastatic germ cell tumors treated with paclitaxel, ifosfamide, and cisplatin vs vinblastine, ifosfamide, and cisplatin as second-line therapy.

Secondary

* Compare the progression-free survival of patients treated with these regimens.
* Compare the toxicity profiles of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior complete response or partial response with negative markers for at least 6 months (yes vs no) and relapse at least 2 years after completing first-line chemotherapy for germ cell tumors (yes vs no). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive paclitaxel IV over 24 hours on day 1 and cisplatin IV over 20-30 minutes and ifosfamide IV over 30 minutes on days 2-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 7-18 OR pegfilgrastim SC once within 24-72 hours after completion of chemotherapy.
* Arm II: Patients receive vinblastine IV on days 1 and 2 and cisplatin IV over 20-30 minutes and ifosfamide IV over 30 minutes on days 1-5. Patients also receive G-CSF SC on days 7-18 OR pegfilgrastim as in arm I.

In both arms, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed germ cell tumor (GCT), including 1 of the following primary tumor sites:

  * Seminoma

    * Testis
    * Retroperitoneum
    * Mediastinum
    * Other extragonadal site
  * Nonseminoma

    * Testis
    * Retroperitoneum
    * Other extragonadal site

      * No tumor of the mediastinum
* Must have evidence of metastatic disease, including either of the following:

  * Unidimensionally measurable lesions

    * At least 20 mm by conventional techniques (e.g., physical exam 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
  * Nonmeasurable lesions, including the following:

    * Small lesions
    * Bone lesions
    * Pleural or pericardial effusions
    * Ascites
    * Irradiated lesions, unless progression is documented after radiotherapy
* Progressive or recurrent disease meeting at least 1 of the following criteria:

  * Measurable progressive disease
  * Biopsy-proven residual disease
  * Persistently elevated or rising ß-human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) titers with no other clear cause for elevation
* Previously treated with 1 and only 1 regimen comprising etoposide and cisplatin with or without bleomycin AND exhibits clinical resistance by at least 1 of the following conditions after therapy\*:

  * Progressive GCT after a partial response to first-line therapy
  * Relapse after complete response (CR) to first-line therapy, including partial response (PR) surgically converted to CR
  * Second testicular primary with evidence of metastases after first-line therapy
  * Relapse after adjuvant chemotherapy NOTE: \*Patients failing to achieve PR or CR with first-line therapy as evidenced by rising markers or new disease within 4 weeks of first-line therapy are not eligible

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Granulocyte count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (transfusion allowed)

Hepatic

* Bilirubin ≤ 1.5 times upper limit of normal\* (ULN)
* AST and ALT ≤ 2.5 times ULN\* NOTE: \*Unless hepatic metastases are present

Renal

* Creatinine ≤ 1.5 times ULN OR
* Creatinine clearance ≥ 50 mL/min

Other

* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior dose-intensive therapy with stem cell replacement

Chemotherapy

* See Disease Characteristics
* At least 3 weeks since prior chemotherapy
* No prior paclitaxel
* No prior docetaxel
* No prior ifosfamide
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* See Disease Characteristics
* At least 3 weeks since prior radiotherapy
* Concurrent or sequential radiotherapy to brain metastases allowed
* No other concurrent palliative radiotherapy

Surgery

* See Disease Characteristics
* Concurrent surgery for brain metastases allowed

Other

* Recovered from prior therapy

Primary outcomes:
measure: Overall survival
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Northeast Alabama Regional Medical Center
state: Alabama
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Naval Medical Center - San Diego
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: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center at Georgetown University Medical 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 Cancer Institute at Memorial Regional Hospital
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: Palm Beach Cancer Institute - West Palm Beach
state: Florida
city: Chicago
country: United States
facility: MBCCOP - University of Illinois at Chicago
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: Evanston
country: United States
facility: CCOP - Evanston
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Incorporated
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Baptist Hospital East - Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Cancer Center - University Campus
state: Massachusetts
city: Saint Joseph
country: United States
facility: Lakeland Cancer Care Center at Lakeland Hospital - 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: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
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: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA - Hooksett
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Cancer Institute of New Jersey at the Cooper University Hospital
state: New Jersey
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: East Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
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: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
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 at University of North Carolina - Chapel Hill
state: North Carolina
city: Concord
country: United States
facility: NorthEast Oncology Associates - Concord
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 Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Pinehurst
country: United States
facility: Comprehensive Cancer Center at Moore Regional Hospital
state: North Carolina
city: Wilmington
country: United States
facility: Zimmer Cancer Center at New Hanover Regional Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Medical Center
state: Oklahoma
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Miriam Hospital at Lifespan
state: Rhode Island
city: Dallas
country: United States
facility: Veterans Affairs Medical Center - Dallas
state: Texas
city: Dallas
country: United States
facility: Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Burlington
country: United States
facility: Vermont Cancer Center at University of Vermont
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, Incorporated - Roanoke
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Medical Center
state: West Virginia
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Robert J. Motzer, MD
role: STUDY_CHAIR
References: