Clinical trial NCT00104676: Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
Official title: A Risk-Adapted Strategy of the Use of Dose-Dense Chemotherapy in Patients With Poor-Prognosis Disseminated Non-Seminomatous Germ Cell Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Extragonadal Germ Cell Tumor
Teratoma
Testicular Germ Cell Tumor
Keywords: stage II malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
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 and teratoma
testicular yolk sac tumor
stage II extragonadal non-seminomatous germ cell tumor
stage III extragonadal non-seminomatous germ cell tumor
testicular immature teratoma
testicular mature teratoma
adult teratoma
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2005-03-04
Enrollment: 263
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 3 trial with direct individual benefit, randomized, open-label, multicenter, parallel groups
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy 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.

PURPOSE: This randomized phase III trial is comparing two different combination chemotherapy regimens to see how well they work in treating patients with stage II or stage III non-seminomatous germ cell tumors.

Detailed description: OBJECTIVES:

* Compare progression-free survival rates of patients with poor prognosis stage II or III non-seminomatous germ cell tumors with an unfavorable decrease of tumor markers after treatment with 1 course of bleomycin, etoposide, and cisplatin followed by subsequent treatment with 3 additional courses of bleomycin, etoposide, and cisplatin OR dose-dense sequential combination chemotherapy.
* Compare overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients with a favorable decrease of tumor markers after 1 course of BEP receive 3 additional courses of BEP. Patients with an unfavorable decrease of tumor markers after 1 course of BEP are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive 3 additional courses of BEP.
* Arm II: Patients receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of non-seminomatous germ cell tumors (NSGCT) as evidenced by 1 of the following criteria:

  * Histologically confirmed NSGCT
  * Clinical evidence of disease AND high serum human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) levels
* Clinical stage II-III disease (disseminated disease)
* Testicular, retroperitoneal, or mediastinal primary site
* Poor prognosis disease, meeting 1 of the following criteria:

  * Mediastinal primary site
  * Non-pulmonary visceral metastases
  * One of the following lab values:

    * HCG \> 50,000 UI/L
    * AFP \> 10,000 ng/mL
    * Lactate dehydrogenase \> 10 times upper limit of normal (ULN)

PATIENT CHARACTERISTICS:

Age

* Over 16

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Absolute granulocyte count ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3

Hepatic

* Bilirubin ≤ 1.5 times ULN

Renal

* Creatinine clearance \> 60 mL/min

Other

* No other prior malignancy except basal cell skin cancer
* No HIV positivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* No prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified

Primary outcomes:
measure: Progression-free Survival Rate After 1 Course of Treatment
timeFrame: 3 years from randomization
Secondary outcomes:
measure: Overall Survival
timeFrame: 3 years from randomization
Other outcomes:
Locations:
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Angers
country: France
facility: Centre Paul Papin
city: Bordeaux
country: France
facility: Institut Bergonie
city: Brest
country: France
facility: C.H.U. de Brest
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
city: Metz
country: France
facility: Hopital Notre-Dame de Bon Secours
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Tenon
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rodez
country: France
facility: Centre Hospitalier de Rodez
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Herblain
country: France
facility: CRLCC Nantes - Atlantique
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Karim Fizazi, MD, PhD
role: STUDY_CHAIR
References:
citation: Fizazi K, Pagliaro L, Laplanche A, Flechon A, Mardiak J, Geoffrois L, Kerbrat P, Chevreau C, Delva R, Rolland F, Theodore C, Roubaud G, Gravis G, Eymard JC, Malhaire JP, Linassier C, Habibian M, Martin AL, Journeau F, Reckova M, Logothetis C, Culine S. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol. 2014 Dec;15(13):1442-1450. doi: 10.1016/S1470-2045(14)70490-5. Epub 2014 Nov 13.