Combination Chemotherapy With or Without Peripheral Stem Cell Transplant in Treating Men With Previously Untreated Germ Cell Cancer

NCT ID: NCT00003941

Last Updated: 2012-09-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

222 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-04-30

Brief Summary

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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

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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.

Conditions

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Mediastinal Cancer Metastatic Cancer Testicular Germ Cell Tumor

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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bleomycin sulfate

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

cisplatin

Intervention Type DRUG

etoposide

Intervention Type DRUG

ifosfamide

Intervention Type DRUG

bone marrow ablation with stem cell support

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

16 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gedske Daugaard, MD, DMSc

Role: STUDY_CHAIR

Rigshospitalet, Denmark

Locations

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Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital

Vienna (Wien), , Austria

Site Status

Institut Jules Bordet

Brussels (Bruxelles), , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

Aarhus University Hospital - Aarhus Sygehus - Norrebrogade

Aarhus, , Denmark

Site Status

Rigshospitalet - Copenhagen University Hospital

Copenhagen, , Denmark

Site Status

Universitaetsklinikum Bonn

Bonn, , Germany

Site Status

Staedtisches Klinikum Dessau

Dessau, , Germany

Site Status

St. Johannes Hospital - Medical Klinik II

Duisburg, , Germany

Site Status

Universitaetsklinikum Essen

Essen, , Germany

Site Status

Staedtische Kliniken Frankfurt am Main - Hoechst

Frankfurt, , Germany

Site Status

Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet

Greifswald, , Germany

Site Status

Universitaetsklinikum Halle

Halle, , Germany

Site Status

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Site Status

Universitaetsklinikum des Saarlandes

Homburg, , Germany

Site Status

Knappschaft Krankenhaus

Langendreer, , Germany

Site Status

Johannes Gutenberg University

Mainz, , Germany

Site Status

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich (Muenchen), , Germany

Site Status

Klinikum Nuernberg - Klinikum Nord

Nuremberg, , Germany

Site Status

Klinikum der Universitaet Regensburg

Regensburg, , Germany

Site Status

Ospedale di Circolo e Fondazione Macchi

Varese, , Italy

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Site Status

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Site Status

University Medical Center Rotterdam at Erasmus Medical Center

Rotterdam, , Netherlands

Site Status

Norwegian Radium Hospital

Oslo, , Norway

Site Status

Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology

Warsaw, , Poland

Site Status

National Cancer Institute - Bratislava

Bratislava, , Slovakia

Site Status

Hospital de la Santa Cruz i Sant Pau

Barcelona, , Spain

Site Status

Institut Catala D'Oncologia

Barcelona, , Spain

Site Status

Hospital Donostia

Donostia / San Sebastian, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Universitario LA FE

Valencia, , Spain

Site Status

Hospital Clinico Universitario Lozano Blesa

Zaragoza, , Spain

Site Status

Inselspital Bern

Bern, , Switzerland

Site Status

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, United Kingdom

Site Status

Countries

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Austria Belgium Denmark Germany Italy Netherlands Norway Poland Slovakia Spain Switzerland United Kingdom

References

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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.

Reference Type RESULT
PMID: 21059637 (View on PubMed)

Other Identifiers

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EORTC-30974

Identifier Type: -

Identifier Source: secondary_id

EORTC-30974

Identifier Type: -

Identifier Source: org_study_id