Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Completed	12 and over	NCI	MSKCC-94076 CLB-99812, E-3894, SWOG-9442, NCI-T94-0086D, NCT00002596, T94-0086

Objectives

1. Compare the efficacy of bleomycin, etoposide, and cisplatin (BEP) with or without high-dose carboplatin, etoposide, and cyclophosphamide plus autologous bone marrow or peripheral blood stem cell transplantation in male patients with poor- or intermediate-risk germ cell tumors.
2. Compare the toxicity of these regimens in these patients.
3. Compare prospectively the prognosis in terms of the rate of decline of the serum tumor markers, human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), in patients treated with these regimens.
4. Correlate hCG and AFP with complete response and survival in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically proven poor-risk, nonseminoma germ cell tumor
  • Must meet 1 of the following 3 conditions:
    • Testis or retroperitoneal primary site without visceral metastasis but with any of the following tumor marker values:
      • Lactic dehydrogenase (LDH) greater than 10 times upper limit of normal (ULN)
      • Human chorionic gonadotropin (hCG) greater than 50,000 IU/L
      • Alpha-fetoprotein (AFP) greater than 10,000 ng/mL
    • Testis or retroperitoneal primary site with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values), including the following:
      • Bone
      • Brain
      • Liver
      • Other nonpulmonary viscera (e.g., skin, spleen)
    • Mediastinal primary site, regardless of presence/absence of visceral metastasis or tumor marker values

  OR




• Histologically proven intermediate-risk, nonseminoma germ cell tumor
  • Testis or retroperitoneal primary site with no visceral metastasis (except lung), and with any of the following tumor marker values:
    • LDH 3-10 times ULN
    • hCG 5,000-50,000 IU/L
    • AFP 1,000-10,000 ng/mL

  OR




• Histologically proven intermediate-risk, seminoma germ cell tumor with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values or primary site), including the following:
  • Bone
  • Brain
  • Liver
  • Other nonpulmonary visceral metastasis (e.g., skin, spleen)



• Histologic confirmation may be delayed, at the discretion of the protocol chairman, until after initiation of study therapy for patients with a testicular mass and elevated AFP or hCG if medical circumstances warrant immediate treatment



• Measurable or evaluable disease



• Concurrent registration on protocol MSKCC-89076 (SWOG-9345) for tumor biology studies required

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 30 days since prior radiotherapy except for brain metastases or documented disease progression
• Recovered from the toxic effects of any prior radiotherapy

Surgery:

• Recovered from the effects of any recent surgery

Patient Characteristics:

Age:

• 12 and over

Sex:

• Male

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• See Disease Characteristics

Renal:

• Creatinine no greater than ULN*

  OR

• Creatinine clearance greater than 50 mL/min*

 [Note: * Abnormal levels due to ureteral obstruction by tumor allowed at the discretion of the protocol chairman]

Other:

• HIV negative
• No other concurrent malignancy except nonmelanomatous skin cancer

Expected Enrollment

A total of 270 patients (135 per treatment arm) will be accrued for this study within 4.4 years.

Outline

This is a randomized, multicenter study. Patients are stratified according to participating center and risk status (poor vs intermediate). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive bleomycin IV on days 1, 8, and 15 and etoposide (VP-16) IV over 30-60 minutes and cisplatin (CDDP) IV over 30-60 minutes on days 1-5 (BEP). Filgrastim (G-CSF) is administered subcutaneously (SC) on days 7-16 or until blood counts recover. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. G-CSF is discontinued 24 hours before initiating subsequent courses of chemotherapy, and withheld on days of bleomycin administration.



• Arm II: Patients receive 2 courses of BEP and G-CSF as in arm I. Patients who have no marrow involvement with tumor undergo harvest of autologous bone marrow before the first or second course of BEP. Patients who have bone marrow involvement with tumor undergo harvest of G-CSF-mobilized autologous peripheral blood stem cells (PBSC) on days 17-21 of the first and/or second courses of BEP. When blood counts recover, patients receive high-dose intensification comprising carboplatin IV over 1 hour, VP-16 IV over 30-60 minutes, and cyclophosphamide IV over 1 hour on days -5 to -3. Autologous bone marrow or PBSC are reinfused over 15-20 minutes on day 0. G-CSF is administered SC beginning 24 hours after transplantation and continuing until blood counts recover. Beginning 1-3 weeks after hospital discharge for the first transplantation and after recovery from any toxic effects, patients with a Karnofsky performance status of 70-100% receive a second course of high-dose intensification plus a second bone marrow or PBSC transplantation in the absence of disease progression or unacceptable toxicity.

Patients on both arms with brain metastases at presentation undergo radiotherapy and/or surgery concurrently with BEP, if medically indicated.

Patients with normal alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG) tumor marker levels after completion of treatment on arm I or II undergo surgical resection of all residual masses. Patients who have no residual malignant tumor or undergo complete resection of only a mature teratoma receive no further therapy. Patients on arm I who undergo complete resection of residual malignant tumor receive 2 additional courses of VP-16 and CDDP without bleomycin. Patients on arm II who undergo complete resection of residual malignant tumor receive no additional chemotherapy. Patients with an unresectable residual malignant tumor receive additional therapy at the discretion of the treating physician. Patients with residual tumor marker (AFP and hCG) positivity after treatment on arm I or II undergo resection of residual masses if tumor marker values fall to normal by marker half-life.

Motzer RJ, Nichols CJ, Margolin KA, et al.: Phase III randomized trial of conventional-dose chemotherapy with or without high-dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line treatment for patients with poor-prognosis metastatic germ cell tumors. J Clin Oncol 25 (3): 247-56, 2007.[PUBMED Abstract]

Bajorin DF, Nichols CR, Margolin KA, et al.: Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): a cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB. [Abstract] J Clin Oncol 24 (Suppl 18): A-4510, 2006.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Robert Motzer, MD, Protocol chair		Ph: 646-422-4312; 800-525-2225

Eastern Cooperative Oncology Group

Patrick Loehrer, MD, Protocol chair		Ph: 317-278-7418; 888-600-4822

Southwest Oncology Group

Kim Margolin, MD, Protocol chair(Contact information may not be current)		Ph: 626-256-4673 ext. 62961; 800-826-4673 Email: kmargolin@coh.org

Cancer and Leukemia Group B

Eric Small, MD, Protocol chair		Ph: 415-353-7095; 800-888-8664

Registry Information
Official Title		RANDOMIZED MULTIINSTITUTIONAL PHASE III TRIAL OF BEP AND HIGH DOSE CHEMOTHERAPY VERSUS BEP ALONE IN PREVIOUSLY UNTREATED PATIENTS WITH POOR RISK GERM CELL TUMORS
Trial Start Date		1994-09-08
Registered in ClinicalTrials.gov		NCT00002596
Date Submitted to PDQ		1994-09-08
Information Last Verified		2003-10-15
NCI Grant/Contract Number		CA05826, CA08748