Clinical trial NCT00002931: Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer
Official title: Tandem High-Dose Chemotherapy With Autologous Stem Cell Rescue for Poor-Prognosis Germ Cell Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Extragonadal Germ Cell Tumor
Ovarian Cancer
Teratoma
Testicular Germ Cell Tumor
Keywords: recurrent malignant testicular germ cell tumor
testicular seminoma
testicular embryonal carcinoma
testicular choriocarcinoma
testicular yolk sac tumor
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and teratoma with seminoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular embryonal carcinoma and seminoma
testicular yolk sac tumor and teratoma
testicular yolk sac tumor and teratoma with seminoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and seminoma
recurrent ovarian germ cell tumor
recurrent extragonadal non-seminomatous germ cell tumor
recurrent extragonadal seminoma
recurrent extragonadal germ cell tumor
adult teratoma
testicular immature teratoma
testicular mature teratoma
ovarian immature teratoma
ovarian mature teratoma
ovarian monodermal and highly specialized teratoma
stage III malignant testicular germ cell tumor
stage IV ovarian germ cell tumor
stage IV extragonadal non-seminomatous germ cell tumor
stage IV extragonadal seminoma
adult central nervous system germ cell tumor
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 48
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bone marrow transplantation or peripheral stem cell transplantation works in treating patients with relapsed germ cell cancer.

Detailed description: OBJECTIVES:

* Estimate the antitumor activity of 2 courses of paclitaxel and carboplatin regimens with autologous stem cell rescue in patients with relapsed germ cell cancer.
* Evaluate the toxic effects of paclitaxel, carboplatin and etoposide (VP-16) with stem cell support followed by paclitaxel, carboplatin and ifosfamide with stem cell support in these patients.

OUTLINE: Patients receive filgrastim (G-CSF) SC or IV 4 days prior to peripheral blood stem cells (PBSC) apheresis. Autologous bone marrow harvest is performed when adequate stem cells cannot be collected.

Patients then receive course 1 of high-dose chemotherapy beginning on day -7 with paclitaxel IV over 24 hours. On days -6 to -4, patients receive etoposide IV over 2 hours and carboplatin (CBDCA) IV over 30 minutes 3 times daily. Following a 2 or 3 week recovery, a second course of chemotherapy begins on day -7, consisting of paclitaxel IV over 24 hours, then CBDCA and ifosfamide on days -6 to -4.

Reinfusion of PBSC and marrow begins on day -2 in both course 1 and 2. In addition, G-CSF IV is given twice a day until 3 consecutive postnadir days of granulocytes of at least 1000/mm\^3 are maintained. On day 0, stem cells with or without bone marrow product are again administered.

Surgery may be performed after course 2 if indicated.

PROJECTED ACCRUAL: The expected accrual rate is 12 patients per year over 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Evaluable germ cell cancer (measurable by radiographic study and/or serum tumor marker elevation) and not curable by standard salvage therapy OR viable cancer on resection of post-chemotherapy residual masses in either intermediate or high risk category
* Bidimensionally measurable disease with measurements performed within 21 days of study entry
* Tumor marker (alpha-fetoprotein, lactate dehydrogenase, beta-human chorionic gonadotropin) studies performed within 7 days prior to study entry

PATIENT CHARACTERISTICS:

Age:

* 16 and over

Performance status:

* Karnofsky 70-100%

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 120,000/mm\^3
* Hemoglobin at least 10 g/dL

Hepatic:

* Bilirubin no greater than 1.6 mg/dL
* SGOT and SGPT no greater than 2 times upper limit of normal (ULN)
* No active hepatitis or cirrhosis

Renal:

* Creatinine clearance at least 70 mL/min

Cardiovascular:

* Ejection fraction (MUGA or echocardiogram) normal
* No EKG evidence of active cardiac disease (arrhythmias, ischemia) which would contraindicate etoposide and paclitaxel study treatment

Pulmonary:

* PaO_2 at least 70 mm Hg
* FEV_1 at least 2 L or 75%
* No history of bleomycin associated or serious lung disease

Neurologic:

* No steroid or glucocorticoid treatment for patients with CNS metastatic disease; at least 1 month with stable post-radiotherapy neurological status and seizure free; if prior seizures, at least 1 month with therapeutic anticonvulsant levels prior to study
* Prior peripheral neuropathy requires consultation with principal investigator

Other:

* No significant active medical illness precluding study or survival
* Not HIV positive
* No prior malignancy within past 5 years except for adequately treated basal cell or squamous cell skin cancer
* No prior hematologic malignancies

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior bone marrow or stem cell rescue with high-dose chemotherapy

Chemotherapy:

* Prior chemotherapy allowed, excluding high-dose therapy with bone marrow or stem cell rescue
* No prior paclitaxel

Endocrine therapy:

* Not specified

Radiotherapy:

* No concurrent radiotherapy during study

Surgery:

* Recovered from prior surgery

Primary outcomes:
measure: Progression-free Survival
timeFrame: Until disease progression, up to 5 years.
measure: Toxic Effects
timeFrame: From date of randomization until death of any cause, assessed up to 12 weeks
Secondary outcomes:
measure: Overall Survival
timeFrame: Until death from any cause, up to 5 years.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Sumanta Pal, MD
role: STUDY_CHAIR
References: