Trial Outcomes & Findings for Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors (NCT NCT00104676)
NCT ID: NCT00104676
Last Updated: 2025-02-06
Results Overview
Primary objective is to compare the progression-free survival of participants after 1 cycle of treatment, treated randomly by 3 additional cycles of BEP (Arm I) or by T-BEP-Oxaliplatin/cisplatin-ifosfamide-Bleomycin (Arm II). The median progression-free survival rate was defined as the median percentage of participants alive without disease progression after 1 course of treatment.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
263 participants
Primary outcome timeframe
3 years from randomization
Results posted on
2025-02-06
Participant Flow
Of the 263 patients registered 255 were evaluated for biomarker decrease after one cycle of BEP. Eight patients were not evaluated for biomarker decrease: 6 patients died early, 1 patient 1 withdrew consent and 1 patient was included by error. 1 patient was not covered by EC approval and excluded froma analysis. The 203 patients with unfavorable decrease in tumor biomarkers were randomized in Arm I (98 patients) or Arm II (105 patients).
Participant milestones
| Measure |
Arm I
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
|---|---|---|
|
Overall Study
STARTED
|
98
|
105
|
|
Overall Study
COMPLETED
|
91
|
91
|
|
Overall Study
NOT COMPLETED
|
7
|
14
|
Reasons for withdrawal
| Measure |
Arm I
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
|---|---|---|
|
Overall Study
Death
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
|
Overall Study
treatment interruption
|
4
|
10
|
Baseline Characteristics
Combination Chemotherapy in Treating Patients With Stage II or Stage III Germ Cell Tumors
Baseline characteristics by cohort
| Measure |
Arm I
n=98 Participants
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
n=105 Participants
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
Total
n=203 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27 Years
n=5 Participants
|
30 Years
n=7 Participants
|
30 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
98 Participants
n=5 Participants
|
105 Participants
n=7 Participants
|
203 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
9 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
9 participants
n=5 Participants
|
9 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
Region of Enrollment
France
|
79 participants
n=5 Participants
|
87 participants
n=7 Participants
|
166 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 years from randomizationPopulation: The primary endpoint for the study was the comparison of the PFS rates in the population of participants with a poor prognostic non-seminomatous germ cell tumors and with an unfavorable decrease in tumor biomarkers, randomized to either Unfav-BEP Control Arm (Arm I) or Unfav-Dose-Dense Arm (Arm II).
Primary objective is to compare the progression-free survival of participants after 1 cycle of treatment, treated randomly by 3 additional cycles of BEP (Arm I) or by T-BEP-Oxaliplatin/cisplatin-ifosfamide-Bleomycin (Arm II). The median progression-free survival rate was defined as the median percentage of participants alive without disease progression after 1 course of treatment.
Outcome measures
| Measure |
Arm I
n=98 Participants
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
n=105 Participants
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
|---|---|---|
|
Progression-free Survival Rate After 1 Course of Treatment
|
48 percentage of participants
Interval 38.0 to 59.0
|
59 percentage of participants
Interval 49.0 to 68.0
|
SECONDARY outcome
Timeframe: 3 years from randomizationTo evaluated the overall survival in both groups in participants presenting fast and slow decrease in serum levels of tumor markers. The median overall survival was defined as the median percentage of participants alive after 1 course of treatment.
Outcome measures
| Measure |
Arm I
n=98 Participants
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
n=105 Participants
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
|---|---|---|
|
Overall Survival
|
65 percentage of participants
Interval 55.0 to 75.0
|
73 percentage of participants
Interval 64.0 to 81.0
|
Adverse Events
Arm I
Serious events: 37 serious events
Other events: 98 other events
Deaths: 61 deaths
Arm II
Serious events: 58 serious events
Other events: 105 other events
Deaths: 66 deaths
Serious adverse events
| Measure |
Arm I
n=98 participants at risk
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
n=105 participants at risk
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukemia
|
2.0%
2/98
|
0.95%
1/105
|
|
Blood and lymphatic system disorders
Anemia
|
5.1%
5/98
|
6.7%
7/105
|
|
Blood and lymphatic system disorders
Aplasia bone marrow
|
3.1%
3/98
|
1.9%
2/105
|
|
Blood and lymphatic system disorders
Bicytopenia
|
0.00%
0/98
|
0.95%
1/105
|
|
Blood and lymphatic system disorders
Febrile aplasia
|
1.0%
1/98
|
4.8%
5/105
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
5.1%
5/98
|
8.6%
9/105
|
|
Blood and lymphatic system disorders
Myeloid leukemia, acute
|
4.1%
4/98
|
0.00%
0/105
|
|
Blood and lymphatic system disorders
Granulocytopenia
|
0.00%
0/98
|
0.95%
1/105
|
|
Blood and lymphatic system disorders
Myelodysplasia
|
0.00%
0/98
|
1.9%
2/105
|
|
Blood and lymphatic system disorders
Neutropenia
|
26.5%
26/98
|
16.2%
17/105
|
|
Blood and lymphatic system disorders
Neutropenia aggravated
|
2.0%
2/98
|
1.9%
2/105
|
|
Blood and lymphatic system disorders
Neutropenia malignany
|
0.00%
0/98
|
0.95%
1/105
|
|
Blood and lymphatic system disorders
Thrombopenia
|
1.0%
1/98
|
6.7%
7/105
|
|
Cardiac disorders
Pericarditis
|
0.00%
0/98
|
0.95%
1/105
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
1/98
|
1.9%
2/105
|
|
Gastrointestinal disorders
Fistula of small intestine
|
1.0%
1/98
|
0.00%
0/105
|
|
Gastrointestinal disorders
Anal abscess
|
0.00%
0/98
|
0.95%
1/105
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.0%
1/98
|
0.95%
1/105
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/98
|
2.9%
3/105
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/98
|
0.95%
1/105
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/98
|
1.9%
2/105
|
|
General disorders
Fever
|
3.1%
3/98
|
4.8%
5/105
|
|
Injury, poisoning and procedural complications
Catheter infection
|
4.1%
4/98
|
2.9%
3/105
|
|
Injury, poisoning and procedural complications
Catheter blocage
|
0.00%
0/98
|
0.95%
1/105
|
|
Gastrointestinal disorders
General physical health deterioration
|
0.00%
0/98
|
0.95%
1/105
|
|
General disorders
Hyperthermia
|
0.00%
0/98
|
1.9%
2/105
|
|
Hepatobiliary disorders
Liver damage
|
0.00%
0/98
|
2.9%
3/105
|
|
Infections and infestations
Infection
|
1.0%
1/98
|
5.7%
6/105
|
|
Infections and infestations
scrotal abscess
|
1.0%
1/98
|
0.00%
0/105
|
|
Infections and infestations
Septicemia
|
1.0%
1/98
|
1.9%
2/105
|
|
Infections and infestations
Sepsis
|
2.0%
2/98
|
4.8%
5/105
|
|
Injury, poisoning and procedural complications
vomiting post chemotherapy
|
0.00%
0/98
|
0.95%
1/105
|
|
Investigations
weight decrease
|
0.00%
0/98
|
0.95%
1/105
|
|
Investigations
Liver enzyme abnormal
|
0.00%
0/98
|
0.95%
1/105
|
|
Metabolism and nutrition disorders
Dehydration
|
1.0%
1/98
|
0.95%
1/105
|
|
Metabolism and nutrition disorders
Diabetes with renal manifestations
|
0.00%
0/98
|
0.95%
1/105
|
|
Metabolism and nutrition disorders
Gout acute
|
0.00%
0/98
|
0.95%
1/105
|
|
Metabolism and nutrition disorders
Malnutrition
|
0.00%
0/98
|
0.95%
1/105
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc compression
|
1.0%
1/98
|
0.00%
0/105
|
|
Musculoskeletal and connective tissue disorders
Lumbar pain
|
1.0%
1/98
|
0.00%
0/105
|
|
Musculoskeletal and connective tissue disorders
Fracture cervical spine
|
0.00%
0/98
|
0.95%
1/105
|
|
Musculoskeletal and connective tissue disorders
Inguinal abscess
|
0.00%
0/98
|
0.95%
1/105
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanoma
|
1.0%
1/98
|
0.95%
1/105
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mediastinal neoplasm NOS
|
0.00%
0/98
|
0.95%
1/105
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor progression
|
1.0%
1/98
|
1.9%
2/105
|
|
Nervous system disorders
Coma
|
1.0%
1/98
|
0.00%
0/105
|
|
Nervous system disorders
Convulsions
|
1.0%
1/98
|
0.00%
0/105
|
|
Nervous system disorders
Hypertension intracranial
|
1.0%
1/98
|
0.00%
0/105
|
|
Nervous system disorders
Consciousness loss of
|
0.00%
0/98
|
0.95%
1/105
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/98
|
0.95%
1/105
|
|
Nervous system disorders
Neuropathy
|
0.00%
0/98
|
4.8%
5/105
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/98
|
2.9%
3/105
|
|
Nervous system disorders
Polyneuropathy toxic
|
0.00%
0/98
|
0.95%
1/105
|
|
Nervous system disorders
Seizure
|
2.0%
2/98
|
5.7%
6/105
|
|
Nervous system disorders
Stroke
|
0.00%
0/98
|
0.95%
1/105
|
|
Psychiatric disorders
Anxiety depression
|
0.00%
0/98
|
0.95%
1/105
|
|
Renal and urinary disorders
Ureteral stricture
|
1.0%
1/98
|
0.95%
1/105
|
|
Renal and urinary disorders
Renal insufficiency
|
0.00%
0/98
|
3.8%
4/105
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/98
|
0.95%
1/105
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.0%
1/98
|
1.9%
2/105
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
1.0%
1/98
|
0.95%
1/105
|
|
Respiratory, thoracic and mediastinal disorders
Obstruction lung disease
|
1.0%
1/98
|
0.00%
0/105
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.0%
2/98
|
3.8%
4/105
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
3.1%
3/98
|
3.8%
4/105
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.0%
1/98
|
0.00%
0/105
|
|
Respiratory, thoracic and mediastinal disorders
Bilateral pneumonia
|
0.00%
0/98
|
0.95%
1/105
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.00%
0/98
|
0.95%
1/105
|
|
Respiratory, thoracic and mediastinal disorders
Mediastinal emphysema
|
0.00%
0/98
|
0.95%
1/105
|
|
Respiratory, thoracic and mediastinal disorders
Pneumopathy
|
0.00%
0/98
|
0.95%
1/105
|
|
Surgical and medical procedures
Platelet transfusion
|
1.0%
1/98
|
0.00%
0/105
|
|
Skin and subcutaneous tissue disorders
Cutaneous hypersensitivity
|
0.00%
0/98
|
0.95%
1/105
|
|
Vascular disorders
Abdominal aortic aneurysm
|
1.0%
1/98
|
0.00%
0/105
|
|
Vascular disorders
Epistaxis
|
1.0%
1/98
|
0.00%
0/105
|
|
Vascular disorders
Intracerebral hemorrhage
|
0.00%
0/98
|
0.95%
1/105
|
|
Vascular disorders
Peritoneal haemorrhage
|
0.00%
0/98
|
0.95%
1/105
|
|
Vascular disorders
Phlebitis lower limb
|
0.00%
0/98
|
0.95%
1/105
|
|
Vascular disorders
Tumor hemorrhage
|
0.00%
0/98
|
0.95%
1/105
|
Other adverse events
| Measure |
Arm I
n=98 participants at risk
Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
|
Arm II
n=105 participants at risk
Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
18.4%
18/98
|
25.7%
27/105
|
|
Gastrointestinal disorders
Nausea
|
73.5%
72/98
|
86.7%
91/105
|
|
Gastrointestinal disorders
Diarrhea
|
20.4%
20/98
|
49.5%
52/105
|
|
Gastrointestinal disorders
Mucositis
|
18.4%
18/98
|
42.9%
45/105
|
|
Hepatobiliary disorders
Liver function test increased
|
43.9%
43/98
|
34.3%
36/105
|
|
Nervous system disorders
Neuropathy
|
21.4%
21/98
|
78.1%
82/105
|
|
Ear and labyrinth disorders
Auditory disorder
|
28.6%
28/98
|
49.5%
52/105
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
34.7%
34/98
|
41.0%
43/105
|
|
Hepatobiliary disorders
Creatinine
|
9.2%
9/98
|
27.6%
29/105
|
|
General disorders
Asthenia
|
77.6%
76/98
|
85.7%
90/105
|
|
Infections and infestations
Infection
|
23.5%
23/98
|
31.4%
33/105
|
|
Blood and lymphatic system disorders
Hemoglobin
|
100.0%
98/98
|
100.0%
105/105
|
|
Blood and lymphatic system disorders
Granulocytes
|
80.6%
79/98
|
80.0%
84/105
|
|
Blood and lymphatic system disorders
Platelets
|
73.5%
72/98
|
83.8%
88/105
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
20.4%
20/98
|
17.1%
18/105
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place