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

Phase 1

Conditions: progressive or recurrent germ cell tumor (measurable or non-measurable)
MedDRA version: 21.1Level: LLTClassification code 10043338Term: Testicular malignant germ cell tumor NOSSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-003930-17-DK

Lead Sponsor: European Organisation for Research and Treatment of Cancer (EORTC)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 420

Inclusion Criteria

- 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 = 14 years (= 15 years in France, = 16 years in Ireland, = 18 years in Germany, Denmark, Switzerland, the Netherlands, Slovenia and Italy)
- ECOG Performance Status 0 to 2
- Male gender
- Required Initial Laboratory Values:
Absolute Neutrophil Count (ANC) = 1,500/mm3
Platelet Count = 100,000/mm3
Calc. 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 2
b. Human T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in Canada and Europe)
c. Hepatitis B surface antigen
d. Hepatitis C antibody
- 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 29
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 378
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

- 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 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.
- Contraindications to the use of paclitaxel, ifosfamide, cisplatine, carboplatine and etoposide as per summary of product characteristics (SPC).