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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00003941
First received: November 1, 1999
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Mediastinal Cancer
Metastatic Cancer
Testicular Germ Cell Tumor
Biological: bleomycin sulfate
Biological: filgrastim
Drug: cisplatin
Drug: etoposide
Drug: ifosfamide
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Failure-free survival as measured by Logrank at 1 year [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • Overall survival as measured by Logrank at 2 years [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Toxicity as measured by NCI-CTC v2.0 after each course, every 6 months up to year 5, and yearly [ Designated as safety issue: Yes ]

Estimated Enrollment: 222
Study Start Date: April 1999
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   16 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003941

  Show 37 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Gedske Daugaard, MD, DMSc Rigshospitalet, Denmark
  More Information

Additional Information:
Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00003941     History of Changes
Other Study ID Numbers: EORTC-30974, EORTC-30974
Study First Received: November 1, 1999
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Mediastinal Neoplasms
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Neoplastic Processes
Pathologic Processes
Thoracic Neoplasms
Neoplasms by Site
Mediastinal Diseases
Thoracic Diseases
Respiratory Tract Diseases
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Bleomycin
Etoposide phosphate
Isophosphamide mustard
Cisplatin
Etoposide
Ifosfamide
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 28, 2014