High-Dose Chemotherapy and Stem Cell Transplant in Treating Patients With Metastatic Germ Cell Tumors That Have Not Responded to First-Line Therapy

NCT ID: NCT01172912

Last Updated: 2013-08-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31

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. An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy.

PURPOSE: This phase II trial is studying the side effects of giving high-dose chemotherapy together with stem cell transplant and to see how well it works in treating patients with metastatic germ cell tumors that have not responded to first-line therapy.

Detailed Description

OBJECTIVES:

• To evaluate the efficacy of high-dose chemotherapy comprising carboplatin and etoposide (CE) in combination with autologous hematopoietic stem cell transplantation using the CE regimen as initial salvage treatment in patients with relapsed or refractory, metastatic germ cell tumors that did not respond to first-line treatment.
• To evaluate the toxicity associated with this regimen in these patients.
• To evaluate biological correlates of outcome in patients with available tissue pre- and post-treatment.

OUTLINE:

• Conventional-dose chemotherapy: Patients receive ifosfamide on days 1 and 2, followed by cisplatin and etoposide on days 3-5, and dexamethasone on days 1-5. Patients undergo leukapheresis daily for stem cell harvest. Patients also receive conventional filgrastim (G-CSF) subcutaneously (SC) once a day beginning 48 hours after completion of chemotherapy until adequate collection of stem cells are obtained. Treatment repeats every 21 days for 1 or 2 courses.
• High-dose (HD) chemotherapy: Patients receive HD carboplatin and etoposide once a day on days 1-3. Treatments repeat every 30-40 days for 2 courses.
• Autologous hematopoietic stem cell transplantation: Patients undergo reinfusion of autologous stem cells on day 6 (after HD chemotherapy on days 1-5). Patients then receive one dose of pegfilgrastim SC beginning 6 hours after completion of stem cell infusion or conventional filgrastim SC once daily beginning 4 days after completion of stem cell infusion and continuing until blood counts recover.

Conditions

Brain and Central Nervous System Tumors; Extragonadal Germ Cell Tumor; Testicular Germ Cell Tumor

Keywords

recurrent extragonadal germ cell tumor; recurrent extragonadal non-seminomatous germ cell tumor; recurrent malignant testicular germ cell tumor; stage IV extragonadal non-seminomatous germ cell tumor; stage III malignant testicular germ cell tumor; recurrent extragonadal seminoma; stage IV extragonadal seminoma; testicular mature teratoma; adult central nervous system germ cell tumor; testicular immature teratoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

pegfilgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cisplatin

Intervention Type: DRUG

dexamethasone

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

ifosfamide

Intervention Type: DRUG

high-dose chemotherapy with autologous stem cell rescue

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed germ cell tumor (GCT) based on pathologic review at INT Milan

• Metastatic disease
• Relapsed or refractory disease
• Prior chemotherapy treatment for GCT without a pathologic diagnosis due to unequivocal clinical evidence of GCT and an urgent need to start therapy (elevated alpha-fetoprotein [AFP] or human chorionic gonadotropin [HCG] with pattern of metastases consistent with GCT and high tumor burden) allowed
• Unequivocal progression of measurable disease, consisting of abnormalities on 2-dimensional imaging or raised tumor markers, following 1 line of cisplatin-based chemotherapy as documented by either of the following:

• Tumor biopsy of new, growing, or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after resection of viable GCT not allowed)
• Increasing or abnormally elevated serum tumor markers (HCG or AFP) (increasing lactate dehydrogenase [LDH] alone does not constitute progressive disease)
• Received ≥ 3 and ≤ 6, cisplatin-based chemotherapy courses as part of first-line (initial) chemotherapy and ≤ 6 cisplatin-based chemotherapy courses
• Brain metastases allowed

• May be treated with radiotherapy and/or surgery concurrently with cisplatin, ifosfamide, and etoposide regimen

• Radiotherapy should not be given concurrently with mobilization phase/leukapheresis and high-dose carboplatin and etoposide

PATIENT CHARACTERISTICS:

• WBC ≥ 2,000/µL
• ANC ≥ 1,500/µL
• Platelet count ≥ 100,000/µL
• Creatinine clearance ≥ 50 cc/min (unless renal dysfunction is due to tumor obstructing the ureters, in which case eligibility will be determined by the principal investigator)
• AST/ALT < 2 times upper limit of normal (ULN) (< 5 times ULN if due to hepatic metastases)
• Total bilirubin < 1.5 times ULN
• Ejection fraction ≥ 50% by echocardiogram
• Negative serology for the following infectious diseases:

• HIV type 1 and 2
• Hepatitis B surface antigen (active carriers)
• Hepatitis C
• Cytomegalovirus (serum Ag p65 ± PCR confirmation at principal investigator discretion)

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior surgery
• At least 3 weeks since prior chemotherapy
• No prior high-dose chemotherapy with peripheral blood stem cell rescue
• No more than 1 prior chemotherapy regimen for metastatic disease

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Principal Investigators

Alessandro M. Gianni, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Locations

Fondazione Istituto Nazionale dei Tumori

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Facility Contacts

Contact Person

Role: primary

Other Identifiers

CDR0000682204

Identifier Type: REGISTRY

Identifier Source: secondary_id

EUDRACT-2010-021898-36

Identifier Type: -

Identifier Source: secondary_id

EU-21054

Identifier Type: -

Identifier Source: secondary_id

ITA-MIL-INT-38-10

Identifier Type: -

Identifier Source: org_study_id