Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Ovarian Cancer, Teratoma, Testicular Germ Cell Tumor
Conditions
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
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.
Interventions
BIOLOGICALfilgrastim
5 ug/kg bid beginning 4 days prior to and continuing through stem cell collection.
DRUGcarboplatin
AUC=7, daily X 3
DRUGetoposide
20 mg/kg by 2 hours infusion daily X 3
DRUGifosfamide
3 gm/m2 IV over 30 minutes X 3 days
DRUGpaclitaxel
425 mg/m2 as 24 hour continuous infusion
PROCEDUREautologous bone marrow transplantation
Given in two divided infusions on day -2 and day 0
PROCEDUREbone marrow ablation with stem cell support
Two cycles of high dose chemotherapy followed by stem cell reinfusion
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Until disease progression, up to 5 years. | Estimated using the product-limit method of Kaplan and Meier. Progression is defined as an increase o any radiologically measureable tumor by greater than 25% or a greater than 10% increase of elevated tumor markers. |
| Toxic Effects | From date of randomization until death of any cause, assessed up to 12 weeks | Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Until death from any cause, up to 5 years. | Estimated using the product-limit method of Kaplan and Meier. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HD Chemo and Auto Stem Cells Cycle 1, stem cell mobilization with granulocyte-colony stimulating factor (G-CSF) at 10 μg/kg/d subcutaneously prior to leukapheresis. G-CSF administration daily during collection until the total collected product excelled 4 × 106 CD34+ cells/kg. 24-hour IV infusion of paclitaxel at 350 mg/m2 or 425 mg/m2 on day -7. Subsequent to this, patients receive etoposide (20 mg/kg IV over 2 hours) and carboplatin (AUC of 7 mg-min/mL IV over 30 minutes) daily on days -6, -5 and -4. IV infusion of 12.5% of the derived CD34+ stem cell product on day -2, followed by administration of 37.5% of the product on day 0. Cycle 2, comprised of paclitaxel, ifosfamide and carboplatin. Ifosfamide administered IV daily at 3 g/m2 over 30 minutes on days -6, -5 and -4. Mesna administered 24 hours subsequently as a 1 g/m2 bolus dose followed by 10g/m2 via continuous IV infusion over 72 hours. The derived CD34+ stem cell product administered in a manner identical to that during Cycle 1 on days -2 and 0. | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | rapidly progressing disease during | 2 |
Baseline characteristics
| Characteristic | HD Chemo and Auto Stem Cells |
|---|---|
| Age, Continuous | 29 years |
| Gender Female | 1 Participants |
| Gender Male | 47 Participants |
| Region of Enrollment United States | 48 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 46 / 48 |
| serious Total, serious adverse events | 1 / 48 |
Outcome results
Primary
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined as an increase o any radiologically measureable tumor by greater than 25% or a greater than 10% increase of elevated tumor markers.
Time frame: Until disease progression, up to 5 years.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HD Chemo and Auto Stem Cells | Progression-free Survival | 11.8 Months |
Primary
Toxic Effects
Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy
Time frame: From date of randomization until death of any cause, assessed up to 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HD Chemo and Auto Stem Cells | Toxic Effects | Hyperbilirubinemia | 3 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Hyperglycemia | 4 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Transaminase alone | 6 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Mucositis/stomatitis | 10 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Nausea/vomiting | 5 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Febrile neutropenia | 1 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Diarrhea | 3 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Fever w/o neutropenia | 2 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Hypocalcemia | 2 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Hemorrhage | 1 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Elevated INR/Prothrombin time | 2 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Renal Failure | 1 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Constipation | 1 participants |
| HD Chemo and Auto Stem Cells | Toxic Effects | Esophagitis | 1 participants |
Secondary
Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
Time frame: Until death from any cause, up to 5 years.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HD Chemo and Auto Stem Cells | Overall Survival | 21.7 Months |