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

Ovarian Cancer Clinical Trial

Official title:

Tandem High-Dose Chemotherapy With Autologous Stem Cell Rescue for Poor-Prognosis Germ Cell Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002931
• Other study ID #: 96126
• Secondary ID: P30CA033572CHNMC
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: December 3, 2014
• Start date: February 1997
• Est. completion date: December 2014

Study information

• Verified date: December 2014
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Extragonadal Germ Cell Tumor
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms
• Ovarian Cancer
• Teratoma
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• filgrastim
5 ug/kg bid beginning 4 days prior to and continuing through stem cell collection.

Drug:
• carboplatin
AUC=7, daily X 3
• etoposide
20 mg/kg by 2 hours infusion daily X 3
• ifosfamide
3 gm/m2 IV over 30 minutes X 3 days
• paclitaxel
425 mg/m2 as 24 hour continuous infusion

Procedure:
• autologous bone marrow transplantation
Given in two divided infusions on day -2 and day 0
• bone marrow ablation with stem cell support
Two cycles of high dose chemotherapy followed by stem cell reinfusion

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antitumor activity		2 years	No
Primary	Toxic effects		2 years	Yes