Clinical trial NCT00301782: Combination Chemotherapy 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Extragonadal Germ Cell Tumor
Teratoma
Testicular Germ Cell Tumor
Keywords: testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma
testicular yolk sac tumor
testicular yolk sac tumor and teratoma
stage I malignant testicular germ cell tumor
stage II malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
recurrent malignant testicular germ cell tumor
recurrent extragonadal non-seminomatous germ cell tumor
stage I extragonadal non-seminomatous germ cell tumor
stage II extragonadal non-seminomatous germ cell tumor
stage III extragonadal non-seminomatous germ cell tumor
stage IV extragonadal non-seminomatous germ cell tumor
recurrent extragonadal germ cell tumor
testicular immature teratoma
testicular mature teratoma
adult teratoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-03-13
Enrollment: 88
Sex: MALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Response rates to treatment
Secondary outcomes:
measure: Overall survival
measure: Progression-free survival
measure: Toxicity
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Inverness
country: United Kingdom
facility: Raigmore Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Robert A. Huddart, MD
role: STUDY_CHAIR
References:
citation: Huddart RA, Gabe R, Cafferty F, et al.: A randomized phase II trial of intensive induction chemotherapy (CBOP/BEP) and standard BEP in poor prognosis germ cell tumors (MRC TE23, CRUK 05/014, ISRCTN53643604). [Abstract] J Clin Oncol 29 (Suppl 15): A-4508, 2011.