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

September 20, 2012 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

222

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna (Wien), Austria, A-1100
        • Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital
  • Belgium
      • Brussels (Bruxelles), Belgium, 1000
        • Institut Jules Bordet
      • Edegem, Belgium, B-2650
        • Universitair Ziekenhuis Antwerpen
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
  • Denmark
      • Aarhus, Denmark, DK-8000
        • Aarhus University Hospital - Aarhus Sygehus - Norrebrogade
      • Copenhagen, Denmark, 2100
        • Rigshospitalet - Copenhagen University Hospital
  • Germany
      • Bochum-Langendreer, Germany, D-44892
        • Knappschaft Krankenhaus
      • Bonn, Germany, D-53105
        • Universitaetsklinikum Bonn
      • Dessau, Germany, D-06822
        • Staedtisches Klinikum Dessau
      • Duisburg, Germany, D-47166
        • St. Johannes Hospital - Medical Klinik II
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Frankfurt, Germany, D-65929
        • Staedtische Kliniken Frankfurt am Main - Hoechst
      • Greifswald, Germany, D-17487
        • Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
      • Halle (Saale), Germany, DOH-06112
        • Universitaetsklinikum Halle
      • Hamburg, Germany, D-20246
        • Universitaetsklinikum Hamburg-Eppendorf
      • Homburg, Germany, D-66421
        • Universitaetsklinikum des Saarlandes
      • Mainz, Germany, D-55101
        • Johannes Gutenberg University
      • Munich (Muenchen), Germany, D-81675
        • Klinikum Rechts der Isar - Technische Universitaet Muenchen
      • Nuernberg, Germany, D-90419
        • Klinikum Nuernberg - Klinikum Nord
      • Regensburg, Germany, D-93053
        • Klinikum der Universitaet Regensburg
  • Italy
      • Varese, Italy, 21100
        • Ospedale di Circolo e Fondazione Macchi
  • Netherlands
      • Leiden, Netherlands, 2300 CA
        • Leiden University Medical Center
      • Maastricht, Netherlands, 6202 AZ
        • Academisch Ziekenhuis Maastricht
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen
      • Rotterdam, Netherlands, 3000 CA
        • University Medical Center Rotterdam at Erasmus Medical Center
  • Norway
      • Oslo, Norway, N-0310
        • Norwegian Radium Hospital
  • Poland
      • Warsaw, Poland, 02 781
        • Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
  • Slovakia
      • Bratislava, Slovakia, 833 10
        • National Cancer Institute - Bratislava
  • Spain
      • Barcelona, Spain, 08907
        • Institut Catala d'Oncologia
      • Barcelona, Spain, 08025
        • Hospital de la Santa Cruz i Sant Pau
      • Malaga, Spain, 29010
        • Hospital Universitario Virgen de la Victoria
      • San Sebastian, Spain, 20014
        • Hospital Donostia
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe
      • Zaragoza, Spain, 50009
        • Hospital Clinico Universitario Lozano Blesa
  • Switzerland
      • Bern, Switzerland, CH-3010
        • Inselspital Bern
  • United Kingdom
    • England
      • Leeds, England, United Kingdom, LS9 7TF
        • Leeds Cancer Centre at St. James's University Hospital
    • Wales
      • Cardiff, Wales, United Kingdom, CF4 7XL
        • Velindre Cancer Center at Velindre Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 48 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Failure-free survival as measured by Logrank at 1 year

Secondary Outcome Measures

Outcome 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
Overall survival as measured by Logrank at 2 years
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
Toxicity as measured by NCI-CTC v2.0 after each course, every 6 months up to year 5, and yearly

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Investigators

  • Study Chair: Gedske Daugaard, MD, DMSc, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 1999

Primary Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

September 24, 2012

Last Update Submitted That Met QC Criteria

September 20, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-30974

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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