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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Tandem High-Dose Chemotherapy (HDCT) With Peripheral-Blood Stem-Cell Rescue for Patients With Metastatic Germ-Cell Tumors Failing First-Line Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01172912
• Other study ID #: ITA-MIL-INT-38-10
• Secondary ID: CDR0000682204EUD
• Status: Recruiting
• Phase: Phase 2
• First received: July 29, 2010
• Last updated: August 9, 2013
• Start date: October 2010

Study information

• Verified date: August 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 47
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Extragonadal Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• filgrastim

• pegfilgrastim

Drug:
• carboplatin

• cisplatin

• dexamethasone

• etoposide

• ifosfamide

Other:
• high-dose chemotherapy with autologous stem cell rescue

• laboratory biomarker analysis

Procedure:
• autologous hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Italy	Fondazione Istituto Nazionale dei Tumori	Milan

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy			No
Primary	Toxicity			Yes
Primary	Biological correlates of outcome			No