A RANDOMIZED PHASE III TRIAL COMPARING CONVENTIONAL-DOSE CHEMOTHERAPY USING PACLITAXEL, IFOSFAMIDE, AND CISPLATIN (TIP) WITH HIGH-DOSE CHEMOTHERAPY USING MOBILIZING PACLITAXEL PLUS IFOSFAMIDE FOLLOWED BY HIGH-DOSE CARBOPLATIN AND ETOPOSIDE (TI-CE) AS FIRST SALVAGE TREATMENT IN RELAPSED OR REFRACTORY GERM CELL TUMORS
- Conditions
- 10038597germ cell tumors
- Registration Number
- NL-OMON52998
- Lead Sponsor
- European Organisation for Research in Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
- Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic
review at the center of enrollment. Tumor may have originated in any primary
site.- Must have evidence of progressive or recurrent GCT (measurable or
non-measurable) following one line of cisplatin-based chemotherapy, defined as
meeting at least one of the following criteria:* Tumor biopsy of new or growing
or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment
on this study for adjuvant treatment after macroscopically complete resection
of viable GCT is not allowed). In the event of an incomplete gross resection
where viable GCT is found, patients will be considered eligible for the study.*
Consecutive elevated serum tumor markers (HCG or AFP) that are increasing.
Increase of an elevated LDH alone does not constitute progressive disease.*
Development of new or enlarging lesions in the setting of persistently elevated
HCG or AFP, even if the HCG and AFP are not continuing to increase.- Must have
received 3-6 cycles of cisplatin-based chemotherapy as part of first-line
(initial) chemotherapy. Prior POMBACE, CBOP-BEP, or GAMEC are allowed.- No more
than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage
chemotherapy).- Must have adequate recovery from prior surgery (e.g., healed
scar, resumption of diet, etc.).- Age >= 18 years- ECOG Performance Status 0 to
2- Male gender- Required Initial Laboratory Values:Absolute Neutrophil Count
(ANC) >= 1,500/mm3Platelet Count >= 100,000/mm3Calc. Creatinine Clearance >= 50
mL/min*Bilirubin <= 2.0 x upper limits of normal (ULN)AST/ALT <= 2.5 x upper
limits of normal (ULN)- Negative Serology (antibody test) for the following
infectious diseases:a. Human Immunodeficiency Virus (HIV) type 1 and 2b. Human
T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in
Canada and Europe)c. Hepatitis B surface antigend. Hepatitis C antibody*
Patients must not present contraindications to the use of paclitaxel,
ifosfamide, cisplatine, carboplatine and etoposide as per summary of product
characteristics (SPC). The investigators must refers to the treatments SPC.*
Reproductive risk: patient must not father a baby while in this study. The
treatment could affect sperm or semen. Therefore, patient and his partner must
use an appropriate and effective contraceptive method during the study period
and for approximately 6 months after taking the last dose of study drug. A
highly effective method of birth control is defined as those which result in
low failure rate (i.e. less than 1% per year) when used consistently.* Before
patient registration/randomization, written informed consent must be given
according to ICH/GCP, and national/local regulations.
- Prior treatment with high-dose chemotherapy (defined as treatment utilizing
stem cell rescue).- Prior treatment with TIP with the exception when given as a
bridge to treatment on protocol for patients with rapidly progressive disease
who cannot wait to complete the eligibility screening process. Only one cycle
is allowed.- Concurrent treatment with other cytotoxic drugs or targeted
therapies.- Radiation therapy (other than to the brain) within 14 days of day 1
of protocol chemotherapy except radiation to brain metastases, which must be
completed 7 days prior to start of chemotherapy.- Previous chemotherapy within
17 days prior to enrollment. A minimum of three weeks after the last day of the
start of the previous chemotherapy regimen before the first day of chemotherapy
on study protocol (e.g., if a patient began their last cycle of BEP on May 1st,
they would be eligible for enrollment on May 19th and could begin treatment on
May 22nd, even if their last day of treatment was May 5th). to Previous
chemotherapy within 16 days prior to enrollment except for bleomycin which
cannot have been given within 5 days prior to enrollment.- Concurrent
malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or
pTis) TCC of the bladder, contralateral GCT, or intratubular germ cell
neoplasia. Patients with a prior malignancy, but at least 2 years since any
evidence of disease are allowed.- Late relapse with completely surgically
resectable disease. Patients with late relapses (defined as relapse >= 2 years
from the date of completion of the last chemotherapy regimen) whose disease is
completely surgically resectable are not eligible. Patients with late relapses
who have unresectable disease are eligible.- Large (>= 2 cm) hemorrhagic or
symptomatic brain metastases until local treatment has been administered
(radiation therapy or surgery). Treatment may begin >= 7 days after completion
of local treatment. Patients with small (< 2 cm) and asymptomatic brain
metastases are allowed and may be treated with radiation therapy and/or surgery
concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically
indicated. Radiation therapy should not be given concurrently with high-dose
carboplatin or etoposide.- Secondary somatic malignancy arising from teratoma
(e.g., teratoma with malignant transformation) when it is actively part of the
disease recurrence or progression.roductief risico: Pa
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To compare the overall survival in patients treated with conventional-dose<br /><br>chemotherapy using the TIP regimen with high-dose chemotherapy (HDCT) plus ASCT<br /><br>using the TI-CE regimen as initial salvage treatment of patients with relapsed<br /><br>or refractory GCT.</p><br>
- Secondary Outcome Measures
Name Time Method