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

August 9, 2013 updated by: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20133
        • Recruiting
        • Fondazione Istituto Nazionale dei Tumori
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Toxicity
Efficacy
Biological correlates of outcome

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Investigators

  • Principal Investigator: Alessandro M. Gianni, MD, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2010

Primary Completion (ANTICIPATED)

October 1, 2012

Study Registration Dates

First Submitted

July 29, 2010

First Submitted That Met QC Criteria

July 29, 2010

First Posted (ESTIMATE)

July 30, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

August 12, 2013

Last Update Submitted That Met QC Criteria

August 9, 2013

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ITA-MIL-INT-38-10
  • CDR0000682204 (REGISTRY: PDQ (Physician Data Query))
  • EUDRACT-2010-021898-36
  • EU-21054

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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