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

Metastatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003941
• Other study ID #: EORTC-30974
• Secondary ID: EORTC-30974
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: September 20, 2012
• Start date: April 1999

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 16 Years to 50 Years

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mediastinal Cancer
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms, Germ Cell and Embryonal
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• bleomycin sulfate

• filgrastim

Drug:
• cisplatin

• etoposide

• ifosfamide

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Austria	Ludwig Boltzmann Institute for Applied Cancer Research at Kaiser Franz Josef Hospital	Vienna (Wien)
Belgium	Institut Jules Bordet	Brussels (Bruxelles)
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Denmark	Aarhus University Hospital - Aarhus Sygehus - Norrebrogade	Aarhus
Denmark	Rigshospitalet - Copenhagen University Hospital	Copenhagen
Germany	Knappschaft Krankenhaus	Bochum-Langendreer
Germany	Universitaetsklinikum Bonn	Bonn
Germany	Staedtisches Klinikum Dessau	Dessau
Germany	St. Johannes Hospital - Medical Klinik II	Duisburg
Germany	Universitaetsklinikum Essen	Essen
Germany	Staedtische Kliniken Frankfurt am Main - Hoechst	Frankfurt
Germany	Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet	Greifswald
Germany	Universitaetsklinikum Halle	Halle (Saale)
Germany	Universitaetsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitaetsklinikum des Saarlandes	Homburg
Germany	Johannes Gutenberg University	Mainz
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich (Muenchen)
Germany	Klinikum Nuernberg - Klinikum Nord	Nuernberg
Germany	Klinikum der Universitaet Regensburg	Regensburg
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	University Medical Center Rotterdam at Erasmus Medical Center	Rotterdam
Norway	Norwegian Radium Hospital	Oslo
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology	Warsaw
Slovakia	National Cancer Institute - Bratislava	Bratislava
Spain	Hospital de la Santa Cruz i Sant Pau	Barcelona
Spain	Institut Catala D'Oncologia	Barcelona
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital Donostia	San Sebastian
Spain	Hospital Universitario LA FE	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Switzerland	Inselspital Bern	Bern
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

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

References & Publications (1)

Daugaard G, Skoneczna I, Aass N, De Wit R, De Santis M, Dumez H, Marreaud S, Collette L, Lluch JR, Bokemeyer C, Schmoll HJ. A randomized phase III study comparing standard dose BEP with sequential high-dose cisplatin, etoposide, and ifosfamide (VIP) plus — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free survival as measured by Logrank at 1 year			No
Secondary	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			No
Secondary	Overall survival as measured by Logrank at 2 years			No
Secondary	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			No
Secondary	Toxicity as measured by NCI-CTC v2.0 after each course, every 6 months up to year 5, and yearly			Yes