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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01172912
First received: July 29, 2010
Last updated: August 9, 2013
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Extragonadal Germ Cell Tumor
Testicular Germ Cell Tumor
Biological: filgrastim
Biological: pegfilgrastim
Drug: carboplatin
Drug: cisplatin
Drug: dexamethasone
Drug: etoposide
Drug: ifosfamide
Other: high-dose chemotherapy with autologous stem cell rescue
Other: laboratory biomarker analysis
Procedure: autologous hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tandem High-Dose Chemotherapy (HDCT) With Peripheral-Blood Stem-Cell Rescue for Patients With Metastatic Germ-Cell Tumors Failing First-Line Treatment

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Efficacy [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Biological correlates of outcome [ Designated as safety issue: No ]

Estimated Enrollment: 47
Study Start Date: October 2010
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01172912

Locations
Italy
Fondazione Istituto Nazionale dei Tumori Recruiting
Milan, Italy, 20133
Contact: Contact Person    39-02-2390-2532    alessandro.gianni@unimi.it   
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Principal Investigator: Alessandro M. Gianni, MD Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01172912     History of Changes
Other Study ID Numbers: ITA-MIL-INT-38-10, CDR0000682204, EUDRACT-2010-021898-36, EU-21054
Study First Received: July 29, 2010
Last Updated: August 9, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Neoplasms by Site
Neoplasms
Nervous System Diseases
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Isophosphamide mustard
Cisplatin
Dexamethasone
Etoposide
Ifosfamide
Carboplatin
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Lenograstim
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 28, 2014