Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors

United Kingdom Research and Innovation (UKRI)

Status and phase: Completed; Phase 2

Conditions: Teratoma; Extragonadal Germ Cell Tumor; Testicular Germ Cell Tumor

Treatments: Drug: vincristine sulfate; Drug: etoposide phosphate; Drug: carboplatin; Drug: cisplatin; Biological: bleomycin sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT00301782

CDR0000456203

EUDRACT-2004-000405-22

EU-205107

ISRCTN53643604

MRC-TE23

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cisplatin, vincristine, bleomycin, carboplatin, and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating germ cell tumors.

PURPOSE: This randomized phase II trial is studying two different combination chemotherapy regimens to compare how well they work in treating male patients with germ cell tumors.

Full description

OBJECTIVES:

Primary

• Compare the response rate in patients with poor-prognosis extracranial nonseminoma germ cell tumors treated with intensive induction chemotherapy comprising cisplatin, vincristine, bleomycin, and carboplatin followed by bleomycin, etoposide phosphate, and cisplatin (BEP) vs standard BEP chemotherapy.

Secondary

• Compare overall and progression-free survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to participating center, pre-protocol low-dose chemotherapy (yes vs no), and other clinically important factors. Patients are randomized to 1 of 2 treatment arms.

• Arm I (BEP): Patients receive bleomycin IV over 15 minutes once on day 1 or 2 and days 8 and 15 and etoposide phosphate IV over 1 hour and cisplatin IV over 4 hours on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

• Arm II (CBOP/BEP): Patients receive chemotherapy according to the following schedule:

  • Weeks 1-6: Patients receive cisplatin IV over 6 hours on days 1, 2, 8, 15, 16, and 22 (OR over 4 hours on days 1-5 and 15-19); vincristine IV on days 1, 8, 15, 22, 29, and 36; bleomycin IV over 15 minutes on days 1, 15, 29, and 36 and bleomycin IV continuously on days 8-12 and 22-25; and carboplatin IV over 30-60 minutes on days 8 and 22.
  • Weeks 7-15: Patients receive bleomycin IV continuously on days 1-5, 8-12, and 15-19 and etoposide phosphate IV over 1 hour and cisplatin IV over 4 hours on days 1-5. Treatment repeats every 21 days for 4 courses.

After completion of study treatment, patients are followed periodically for 5 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 88 patients will be accrued for this study.

Enrollment: 88 estimated patients

Sex: Male

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Nonseminoma germ cell tumor of any extracranial primary site diagnosed by 1 of the following methods:

  • Histologic confirmation
  • Alpha-fetoprotein (AFP) > 1,000 ng/mL or human chorionic gonadotropin (hCG) > 5,000 IU/L with appropriate clinical picture in a man < 45 years of age

• Poor prognosis features as defined by ≥ 1 of the following:

  • AFP > 10,000 ng/mL
  • hCG > 50,000 IU/L
  • Lactic dehydrogenase > 10 times normal
  • Nonpulmonary visceral metastases
  • Mediastinal primary site

PATIENT CHARACTERISTICS:

• Male

• WHO performance status 0-3

• Glomerular filtration rate > 50 mL/min

  • Less than 50 mL/min eligible if due to obstructive neuropathy that can be relieved by stenting or nephrostomy

• No comorbid condition that would prevent treatment

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy except low-dose chemotherapy to stabilize disease before study therapy