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Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer

Primary Purpose

Brain and Central Nervous System Tumors, Extragonadal Germ Cell Tumor, Ovarian Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
carboplatin
etoposide
ifosfamide
paclitaxel
autologous bone marrow transplantation
bone marrow ablation with stem cell support
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

16 Years - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HD Chemo and Auto Stem Cells

Arm Description

Outcomes

Primary Outcome Measures

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.
Toxic Effects
Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy

Secondary Outcome Measures

Overall Survival
Estimated using the product-limit method of Kaplan and Meier.

Full Information

First Posted
November 1, 1999
Last Updated
January 6, 2017
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002931
Brief Title
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

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
February 1997 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HD Chemo and Auto Stem Cells
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
5 ug/kg bid beginning 4 days prior to and continuing through stem cell collection.
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
AUC=7, daily X 3
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Description
20 mg/kg by 2 hours infusion daily X 3
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Description
3 gm/m2 IV over 30 minutes X 3 days
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Intervention Description
425 mg/m2 as 24 hour continuous infusion
Intervention Type
Procedure
Intervention Name(s)
autologous bone marrow transplantation
Intervention Description
Given in two divided infusions on day -2 and day 0
Intervention Type
Procedure
Intervention Name(s)
bone marrow ablation with stem cell support
Intervention Description
Two cycles of high dose chemotherapy followed by stem cell reinfusion
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
Title
Toxic Effects
Description
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
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Estimated using the product-limit method of Kaplan and Meier.
Time Frame
Until death from any cause, up to 5 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sumanta Pal, MD
Organizational Affiliation
City of Hope Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States

12. IPD Sharing Statement

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Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Relapsed Germ Cell Cancer

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