Clinical trial NCT00003941: Combination Chemotherapy With or Without Peripheral Stem Cell Transplant in Treating Men With Previously Untreated Germ Cell Cancer
Official title: A Randomized Phase III Study of Sequential High-Dose Cisplatinum/Etoposide/Ifosfamide Plus Stem Cell Support Versus BEP in Patients With Poor Prognosis Germ Cell Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Mediastinal Cancer
Metastatic Cancer
Testicular Germ Cell Tumor
Keywords: stage III malignant testicular germ cell tumor
mediastinal cancer
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
tumors metastatic to brain
liver metastases
bone metastases
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 222
Sex: MALE
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy and kill more cancer cells. It is not yet known whether chemotherapy and peripheral stem cell transplant is more effective than chemotherapy alone.

PURPOSE: This randomized phase III trial is studying how well combination chemotherapy works when given with peripheral stem cell transplant and how it compares with combination chemotherapy alone in treating men with previously untreated germ cell cancer.

Detailed description: OBJECTIVES:

* Compare the efficacy of standard cisplatin, etoposide, and ifosfamide (VIP) followed by sequential high-dose VIP and stem cell rescue versus bleomycin, etoposide, and cisplatin (BEP) in men with previously untreated poor-prognosis germ cell cancer.
* Compare the acute and late toxicities of these treatment regimens in this patient population.
* Compare these regimens in terms of failure-free survival, response rate, and overall survival in these patients.
* Evaluate the quality of life in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center, primary mediastinal germ cell tumor (yes vs no), and nonpulmonary visceral metastases (liver vs bone vs brain). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive etoposide IV over 1 hour followed by cisplatin IV over 1 hour on days 1-5 and bleomycin IV over 30 minutes on days 2, 8, and 15. Treatment repeats every 3 weeks for 4 courses.
* Arm II: Patients receive 1 course of standard dose chemotherapy consisting of etoposide IV over 1 hour followed by cisplatin IV over 1 hour and ifosfamide IV over 1 hour on days 1-5. Peripheral blood stem cells (PBSC) are harvested around day 12-15. Patients also receive daily filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until PBSC collection is complete.

After day 21, patients receive high-dose chemotherapy consisting of etoposide IV over 1 hour followed by cisplatin IV over 1 hour, and ifosfamide IV over 1 hour on days -6 through -2. PBSCs are infused on day 0. Patients receive daily G-CSF subcutaneously beginning on day 1 and continuing through day 19 or until blood counts have recovered. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before chemotherapy, at 6 months, and at 2 years after treatment.

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

PROJECTED ACCRUAL: A total of 222 patients (111 per treatment arm) will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven germ cell cancer

  * Nonseminoma OR
  * Combined seminoma and nonseminoma
* Poor prognosis (nonseminoma):

  * Testis/retroperitoneal primary AND
  * One of the following poor tumor markers

    * AFP greater than 10,000 iu/L
    * HCG greater than 50,000 iu/L
    * LDH greater than 10 times upper limit of normal OR
  * Nonpulmonary visceral metastases (i.e., liver, bone, or brain) OR
  * Mediastinal primary

PATIENT CHARACTERISTICS:

Age:

* 16 to 50

Sex:

* Male

Performance status:

* WHO 0-3

Life expectancy:

* Not specified

Hematopoietic:

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

Hepatic:

* Bilirubin no greater than 1.25 times upper limit of normal (ULN)
* AST no greater than 2 times ULN

Renal:

* Creatinine clearance at least 60 mL/min (unless due to obstructive uropathy correctable by nephrostomy)

Other:

* No other malignancy except basal cell skin cancer
* No neuropathy
* No other serious illness or medical condition
* No psychological, familial, sociological, or geographical condition that would prevent compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* Concurrent radiotherapy for brain metastases allowed

Surgery:

* Concurrent surgery for brain metastases allowed

Primary outcomes:
measure: Failure-free survival as measured by Logrank at 1 year
Secondary outcomes:
measure: Complete response as measured by negative tumor markers and no residual masses or viable cancer cells at the end of CT scan or debulking surgery
measure: Overall survival as measured by Logrank at 2 years
measure: Quality of life as measured by Quality of Life Questionnaire-Core 30 (QLQ-C30) v3.0 at baseline, at month 6, and at year 2
measure: Toxicity as measured by NCI-CTC v2.0 after each course, every 6 months up to year 5, and yearly
Other outcomes:
Locations:
city: Vienna (Wien)
country: Austria
facility: Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Aarhus
country: Denmark
facility: Aarhus University Hospital - Aarhus Sygehus - Norrebrogade
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Copenhagen University Hospital
city: Bochum-Langendreer
country: Germany
facility: Knappschaft Krankenhaus
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Dessau
country: Germany
facility: Staedtisches Klinikum Dessau
city: Duisburg
country: Germany
facility: St. Johannes Hospital - Medical Klinik II
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Frankfurt
country: Germany
facility: Staedtische Kliniken Frankfurt am Main - Hoechst
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Halle (Saale)
country: Germany
facility: Universitaetsklinikum Halle
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Munich (Muenchen)
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Nuernberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Rotterdam
country: Netherlands
facility: University Medical Center Rotterdam at Erasmus Medical Center
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
city: Barcelona
country: Spain
facility: Hospital de la Santa Cruz i Sant Pau
city: Barcelona
country: Spain
facility: Institut Catala D'Oncologia
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: San Sebastian
country: Spain
facility: Hospital Donostia
city: Valencia
country: Spain
facility: Hospital Universitario LA FE
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Rigshospitalet, Denmark
name: Gedske Daugaard, MD, DMSc
role: STUDY_CHAIR
References:
citation: Daugaard G, Skoneczna I, Aass N, De Wit R, De Santis M, Dumez H, Marreaud S, Collette L, Lluch JRG, Bokemeyer C, Schmoll HJ. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus stem-cell support in males with poor-prognosis germ-cell cancer. An intergroup study of EORTC, GTCSG, and Grupo Germinal (EORTC 30974). Ann Oncol. 2011 May;22(5):1054-1061. doi: 10.1093/annonc/mdq575. Epub 2010 Nov 8.