Combination Chemotherapy in Treating Men With Germ Cell Cancer

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00003643

Collaborator

(none)

498

Enrollment

Locations

7.2

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Extragonadal Germ Cell Tumor Teratoma Testicular Germ Cell Tumor	Biological: bleomycin sulfate Biological: filgrastim Drug: cisplatin Drug: etoposide Drug: paclitaxel	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

498 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Randomized Phase II/III Study of Taxol/Paclitaxel-BEP Versus BEP in Patients With Intermediate Prognosis Germ Cell Cancer

Study Start Date :

Oct 1, 1998

Outcome Measures

Primary Outcome Measures

Failure-free survival as measured by Logrank []

Secondary Outcome Measures

Response to treatment as measured by normalized markers without residual viable cancer after CT scan or surgery []
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 []
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 []
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 []
Quality of life as measured by Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, during treatment, and at years 1 and 2 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital	Vienna		Austria	A-1100
2	Institut Jules Bordet	Brussels		Belgium	1000
3	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	B-2650
4	U.Z. Gasthuisberg	Leuven		Belgium	B-3000
5	Aarhus Universitetshospital - Aarhus Sygehus	Aarhus		Denmark	DK-8000
6	Rigshospitalet - Copenhagen University Hospital	Copenhagen		Denmark	2100
7	Centre Regional Francois Baclesse	Caen		France	14076
8	Institut Claudius Regaud	Toulouse		France	31052
9	Institut Gustave Roussy	Villejuif		France	F-94805
10	Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin		Germany	D-12200
11	Universitaetsklinikum Bonn	Bonn		Germany	D-53105
12	St. Johannes Hospital - Medical Klinik II	Duisburg		Germany	D-47166
13	Universitaetsklinikum Essen	Essen		Germany	D-45122
14	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald		Germany	D-17487
15	Allgemeines Krankenhaus Hagen	Hagen		Germany	D-58095
16	Universitaetsklinikum Halle	Halle		Germany	DOH-06112
17	University Medical Center Hamburg - Eppendorf	Hamburg		Germany	D-20246
18	Universitaetsklinikum des Saarlandes	Homburg		Germany	D-66421
19	Klinikum Kassel	Kassel		Germany	D-34125
20	Klinikum der Stadt Ludwigshafen am Rhein	Ludwigshafen am Rhein		Germany	D-67063
21	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg		Germany	D-39120
22	Klinikum der Stadt Mannheim	Mannheim		Germany	D-68135
23	Universitaetsklinikum Giessen und Marburg GmbH - Marburg	Marburg		Germany	D-35033
24	Medizinische Klinik und Poliklinik A - Universitaetsklinikum Muenster	Muenster		Germany	D-48149
25	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich		Germany	D-81675
26	Klinikum Nuernberg - Klinikum Nord	Nuremberg		Germany	D-90419
27	Klinikum der Universitaet Regensburg	Regensburg		Germany	D-93053
28	Klinikum Schwerin	Schwerin		Germany	D-19049
29	Southwest German Cancer Center at Eberhard-Karls-University	Tuebingen		Germany	D-72076
30	National Institute of Oncology	Budapest		Hungary	1125
31	Assaf Harofeh Medical Center	Zerifin		Israel	70300
32	Ospedale di Circolo e Fondazione Macchi	Varese		Italy	21100
33	Jeroen Bosch Ziekenhuis	's-Hertogenbosch		Netherlands	5211 NL
34	Academisch Medisch Centrum at University of Amsterdam	Amsterdam		Netherlands	1105 AZ
35	Leiden University Medical Center	Leiden		Netherlands	2300 CA
36	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen		Netherlands	NL-6500 HB
37	University Medical Center Rotterdam at Erasmus Medical Center	Rotterdam		Netherlands	3000 CA
38	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam		Netherlands	3008 AE
39	University Medical Center Utrecht	Utrecht		Netherlands	3584 CX
40	Norwegian Radium Hospital	Oslo		Norway	N-0310
41	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology - Warsaw	Warsaw		Poland	02 781
42	National Cancer Institute - Bratislava	Bratislava		Slovakia	833 10
43	Hospital de la Santa Cruz i Sant Pau	Barcelona		Spain	08025
44	Vall d'Hebron University Hospital	Barcelona		Spain	08035
45	Institut Catala D'Oncologia	Barcelona		Spain	08907
46	Hospital Universitario San Carlos	Madrid		Spain	28040
47	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
48	Hospital Universitario Virgen de la Victoria	Malaga		Spain	29010
49	Hospital Sant Joan de Reus	Reus		Spain	43201
50	Hospital Universidad Virgen Del Rocio	Sevilla		Spain	E- 41013
51	Hospital Universitario La Fe	Valencia		Spain	46009
52	Hospital Clinico Universitario Lozano Blesa	Zaragoza		Spain	50009
53	Addenbrooke's Hospital	Cambridge	England	United Kingdom	CB2 2QQ
54	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England	United Kingdom	GL53 7AN
55	Leeds Cancer Centre at St. James's University Hospital	Leeds	England	United Kingdom	LS9 7TF
56	Saint Bartholomew's Hospital	London	England	United Kingdom	EC1A 7BE
57	University College Hospital - London	London	England	United Kingdom	WC1E 6AU
58	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
59	Nottingham City Hospital NHS Trust	Nottingham	England	United Kingdom	NG5 1PB
60	Rosemere Cancer Centre at Royal Preston Hospital	Preston	England	United Kingdom	PR2 9HT
61	Berkshire Cancer Centre at Royal Berkshire Hospital	Reading	England	United Kingdom	RG1 5AN
62	Cancer Research Centre at Weston Park Hospital	Sheffield	England	United Kingdom	S1O 2SJ
63	Royal South Hants Hospital	Southampton	England	United Kingdom	SO14 0YG
64	Royal Marsden - Surrey	Sutton	England	United Kingdom	SM2 5PT
65	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England	United Kingdom	SS0 0RY
66	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
67	Western Infirmary	Glasgow	Scotland	United Kingdom	G11 6NT
68	Gartnavel General Hospital	Glasgow	Scotland	United Kingdom	G12 0YN
69	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales	United Kingdom	CF4 7XL