Combination Chemotherapy in Treating Male Patients With Germ Cell Tumors

Condition(s) targeted: Extragonadal Germ Cell Tumor; Teratoma; Testicular Germ Cell Tumor

Intervention: bleomycin sulfate (Biological); carboplatin (Drug); cisplatin (Drug); etoposide phosphate (Drug); vincristine sulfate (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Medical Research Council

Official(s) and/or principal investigator(s):
Robert A. Huddart, MD, Study Chair, Affiliation: Royal Marsden NHS Foundation Trust

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.

Official title: Randomized Phase II Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP Chemotherapy in Poor Prognosis Male Germ Cell Tumors

Study design: Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Response rates to treatment

Secondary outcome:

Overall survival

Progression-free survival

Toxicity

Detailed 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.

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Male.

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

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust, Birmingham, England B15 2TH, United Kingdom

Bristol Haematology and Oncology Centre, Bristol, England BS2 8ED, United Kingdom

Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom

Gloucestershire Oncology Centre at Cheltenham General Hospital, Cheltenham, England GL53 7AN, United Kingdom

Walsgrave Hospital, Coventry, England CV2 2DX, United Kingdom

Royal Devon and Exeter Hospital, Exeter, England EX2 5DW, United Kingdom

Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom

Leicester Royal Infirmary, Leicester, England LE1 5WW, United Kingdom

Saint Bartholomew's Hospital, London, England EC1A 7BE, United Kingdom

University College of London Hospitals, London, England WIT 3AA, United Kingdom

Christie Hospital, Manchester, England M20 4BX, United Kingdom

Clatterbridge Centre for Oncology, Merseyside, England CH63 4JY, United Kingdom

Nottingham City Hospital, Nottingham, England NG5 1PB, United Kingdom

Rosemere Cancer Centre at Royal Preston Hospital, Preston, England PR2 9HT, United Kingdom

Berkshire Cancer Centre at Royal Berkshire Hospital, Reading, England RG1 5AN, United Kingdom

Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom

Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom

Beatson West of Scotland Cancer Centre, Glasgow, Scotland G11 6NT, United Kingdom

Raigmore Hospital, Inverness, Scotland 1V2 3UJ, United Kingdom

Velindre Cancer Center at Velindre Hospital, Cardiff, Wales CF14 2TL, United Kingdom

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2005
Last updated: August 23, 2013