Clinical trial NCT00003643: Combination Chemotherapy in Treating Men With Germ Cell Cancer
Official title: Randomized Phase II/III Study of Taxol/Paclitaxel-BEP Versus BEP in Patients With Intermediate Prognosis Germ Cell Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Extragonadal Germ Cell Tumor
Teratoma
Testicular Germ Cell Tumor
Keywords: stage III malignant testicular germ cell tumor
testicular seminoma
testicular embryonal carcinoma
testicular choriocarcinoma
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
stage IV extragonadal non-seminomatous germ cell tumor
stage IV extragonadal seminoma
testicular immature teratoma
testicular mature teratoma
adult teratoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 498
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 tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy may be more effective for germ cell cancer.

PURPOSE: This randomized phase II/III trial is studying two different regimens of combination chemotherapy and comparing how well they work in treating men with germ cell cancer.

Detailed description: OBJECTIVES:

Phase II

* Compare the complete response rates in men with intermediate prognosis germ cell cancer treated with bleomycin, cisplatin, and etoposide (BEP) vs bleomycin, cisplatin, etoposide, and paclitaxel (T-BEP).
* Define the toxicity profile of T-BEP in these patients.

Phase III

* Compare the disease-free survival of patients treated with these regimens.
* Compare the complete response rates and overall survival of patients treated with these regimens.
* Compare symptoms and aspects of quality of life at baseline and after treatment in patients treated with these regimens.
* Compare the acute and intermediate (1-2 years) side effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (seminoma vs non-seminoma) and hospital. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive cisplatin IV and etoposide IV on days 1-5 and bleomycin IV on days 1, 8, and 15.
* Arm II: Patients receive cisplatin, etoposide, and bleomycin as in arm I and paclitaxel IV over 3 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 6-15.

In both arms, treatment repeats every 3 weeks for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before treatment randomization and at 1 and 2 years after randomization.

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 then annually thereafter.

PROJECTED ACCRUAL: A total of 84-164 patients (42-82 per treatment arm) will be accrued for the phase II study. A total of 498 patients (249 per treatment arm) will be accrued for the phase III study. Accrual will be completed within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven germ cell cancer

  * Seminoma
  * Non-seminoma
  * Combined
* Intermediate prognosis

  * Non-seminoma:

    * Testis/retroperitoneal primary
    * No non-pulmonary visceral metastases
    * Meets 1 of the following criteria:

      * Alpha-fetoprotein (AFP) 1,000- 10,000 IU/L
      * Human chorionic gonadotropin (hCG) 5,000-50,000 IU/L
      * Lactic dehydrogenase (LDH) 1.5 times-10 times upper limit of normal (ULN)
  * Seminoma:

    * Any primary site
    * Any LDH and HCG
    * AFP normal
    * Non-pulmonary visceral metastases present

PATIENT CHARACTERISTICS:

Age:

* 16 to 50

Sex:

* Male

Performance status:

* WHO 0-2

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 ULN
* AST no greater than 2 times ULN

Renal:

* Creatinine clearance at least 40 mL/min (unless due to obstructive uropathy which can be relieved by nephrostomy)

Other:

* No pre-existing neuropathy
* No other malignancy except basal cell skin cancer
* No other serious illness or medical conditions incompatible with the protocol

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* Not specified

Surgery:

* Not specified

Primary outcomes:
measure: Failure-free survival as measured by Logrank
Secondary outcomes:
measure: Response to treatment as measured by normalized markers without residual viable cancer after CT scan or surgery
measure: Overall survival as measured by Logrank at end of each course, at 6 weeks after completion of study treatment, every 6 months up to year 5, and then annually thereafter
measure: Disease-free survival as measured by Logrank at end of each course, at 6 weeks after completion of study treatment, every 6 months up to year 5, and then annually thereafter
measure: Toxicity as measured by NCI-CTC v2.0 at end of each course, at 6 weeks after completion of study treatment, every 6 months up to year 5, and then annually thereafter
measure: Quality of life as measured by Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, during treatment, and at years 1 and 2
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
city: Brussels
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 Universitetshospital - Aarhus Sygehus
city: Copenhagen
country: Denmark
facility: Rigshospitalet - Copenhagen University Hospital
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Bonn
country: Germany
facility: Universitaetsklinikum Bonn
city: Duisburg
country: Germany
facility: St. Johannes Hospital - Medical Klinik II
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Hamburg
country: Germany
facility: University Medical Center Hamburg - Eppendorf
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Ludwigshafen am Rhein
country: Germany
facility: Klinikum der Stadt Ludwigshafen am Rhein
city: Magdeburg
country: Germany
facility: Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
city: Mannheim
country: Germany
facility: Klinikum der Stadt Mannheim
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH - Marburg
city: Muenster
country: Germany
facility: Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Nuremberg
country: Germany
facility: Klinikum Nuernberg - Klinikum Nord
city: Regensburg
country: Germany
facility: Klinikum der Universitaet Regensburg
city: Schwerin
country: Germany
facility: Klinikum Schwerin
city: Tuebingen
country: Germany
facility: Southwest German Cancer Center at Eberhard-Karls-University
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
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: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw
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: Vall d'Hebron University Hospital
city: Barcelona
country: Spain
facility: Institut Catala D'Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
city: Sevilla
country: Spain
facility: Hospital Universidad Virgen Del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: University College Hospital - London
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Royal South Hants Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center
name: Ronald De Wit, MD, PhD
role: STUDY_CHAIR
References: