Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, ifosfamide, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy with or without radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with stage III or stage IV malignant peripheral nerve sheath tumors.

Condition	Intervention	Phase
Neurofibromatosis Type 1 Sarcoma	Biological: filgrastim Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Procedure: conventional surgery Radiation: radiation therapy	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Malignant Peripheral Nerve Sheath Tumors

Resource links provided by NLM:

Genetics Home Reference related topics: neurofibromatosis type 1 neurofibromatosis type 2

MedlinePlus related topics: Neurofibromatosis

Genetic and Rare Diseases Information Center resources: Soft Tissue Sarcoma Neurofibromatosis Type 1 Neurofibromatosis Neurofibroma Malignant Peripheral Nerve Sheath Tumor Neurofibrosarcoma Schwannoma Carcinoid Tumor Neuroepithelioma Fibrosarcoma

U.S. FDA Resources

Further study details as provided by Sarcoma Alliance for Research through Collaboration:

Primary Outcome Measures:

Response rate (complete response and partial response) [ Time Frame: After 4 Cycles (1 cycle=21 days) ]


Enrollment:	74
Study Start Date:	December 2005
Study Completion Date:	June 2014
Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Chemotherapy and local control by radiotherapy and surgery Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.	Biological: filgrastim Given subcutaneously Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: ifosfamide Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy
Experimental: Chemotherapy and local control by surgery Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.	Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: ifosfamide Given IV Procedure: conventional surgery Patients undergo surgery

Arms

Assigned Interventions

Experimental: Chemotherapy and local control by radiotherapy and surgery

Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course. After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.

Biological: filgrastim

Given subcutaneously

Drug: doxorubicin hydrochloride

Given IV

Drug: etoposide

Given IV

Drug: ifosfamide

Given IV

Procedure: conventional surgery

Patients undergo surgery

Radiation: radiation therapy

Patients undergo radiotherapy

Experimental: Chemotherapy and local control by surgery

Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.

Drug: doxorubicin hydrochloride

Given IV

Drug: etoposide

Given IV

Drug: ifosfamide

Given IV

Procedure: conventional surgery

Patients undergo surgery

Detailed Description:

OBJECTIVES:

Primary

Determine the clinical response rate (complete and partial) in patients with sporadic or neurofibromatosis type 1 (NF1)-associated high-grade stage III or IV malignant peripheral nerve sheath tumors (MPNSTs) after treatment with 4 courses of chemotherapy comprising doxorubicin hydrochloride and ifosfamide (IA) followed by etoposide and ifosfamide (IE).

Secondary

Evaluate the utility of fludeoxyglucose F18 positron emission tomography (^18FDG-PET) and automated MRI volumetric tumor analysis as tools to assess response to treatment.
Correlate response evaluation by 2-dimensional WHO criteria, 1-dimensional RECIST criteria, ^18FDG-PET, and volumetric MRI with percent necrosis in tumor specimens from patients who undergo surgery for local control after chemotherapy.
Evaluate the response of plexiform neurofibroma(s) (if present) to chemotherapy using WHO criteria and automated volumetric MRI analysis.
Evaluate the molecular biology of sporadic and NF1-associated MPNSTs by performing a detailed pathologic analysis of tumor samples with the goal to analyze if markers can be identified that predict for response to chemotherapy or outcome.
Construct a tissue microarray from submitted tumor samples, that will be used in the future to identify novel targets for treatment of MPNSTs.
Assess if a serum biomarker can be identified, that predicts for the presence of a MPNST versus benign plexiform neurofibroma.
Increase the knowledge of the epidemiology and clinical presentation of NF1-associated MPNSTs.

OUTLINE: This is a multicenter study. Patients are stratified according to type of malignant peripheral nerve sheath tumor (MPNST) (sporadic MPNST vs neurofibromatosis type 1 [NF1]-associated MPNST). Patients receive 1 of 2 treatment regimens depending on the location of the MPNST and tumor response to chemotherapy.

Chemotherapy and local control by radiotherapy and surgery: Patients receive doxorubicin hydrochloride and ifosfamide (IA) chemotherapy comprising doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 and ifosfamide IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity. Patients then receive etoposide and ifosfamide (IE) chemotherapy comprising etoposide IV over 1 hour and ifosfamide IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously (SC) after each chemotherapy course beginning on day 6 or 7 and continuing until blood counts recover or pegfilgrastim SC once on day 6 or 7.

After recovery from chemotherapy, patients undergo radiotherapy and receive 2 more courses of IE during radiotherapy followed by 2 more courses of IA after completion of radiotherapy. Some patients may then undergo surgery.

Chemotherapy and local control by surgery: Patients receive 2 courses of IA followed by 2 courses of IE as above. After recovery from chemotherapy, patients undergo surgery. After recovery from surgery, patients receive 2 more courses of IA followed by 2 more courses of IE in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 74 patients will be accrued for this study.

Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Newly diagnosed sporadic or neurofibromatosis type 1 (NF1)-associated high-grade malignant peripheral nerve sheath tumors (MPNSTs)
- Stage III or stage IV (metastatic) disease
Measurable disease, defined as at least 1 tumor that is measurable in 2 dimensions on CT scan or MRI

PATIENT CHARACTERISTICS:

Ejection fraction normal by echocardiogram or MUGA
Serum creatinine normal for age OR creatinine clearance > 60 mL/min
SGPT < 5 times upper limit of normal (ULN)
Bilirubin < 2.5 times ULN
Absolute neutrophil count ≥ 1,500/mm^3*
Hemoglobin ≥ 9.0 g/dL*
Platelet count ≥ 100,000/mm^3*
ECOG performance status 0-2
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study treatment NOTE: * Unsupported

PRIOR CONCURRENT THERAPY:

No prior chemotherapy for MPNST
Prior surgical resection of MPNST allowed provided residual or recurrent measurable disease is present
Recovered from toxic effects of all prior therapy
At least 3 weeks since prior chemotherapy or biologic therapy for treatment of a plexiform neurofibroma, optical pathway tumor, or other NF1-associated tumor (in patients with NF1)
At least 6 weeks since prior radiotherapy for treatment of a plexiform neurofibroma, optical pathway tumor, or other NF1-associated tumor (in patients with NF1)
At least 4 weeks since prior radiotherapy to the area involved by MPNST
No other concurrent growth factors (e.g., sargramostim [GM-CSF] or interleukin-11)
- Concurrent epoetin alfa allowed

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: NCT00304083

Locations


United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, California
Sarcoma Oncology Center
Santa Monica, California, United States, 90403
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202-5289
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0942
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, North Carolina
Carolinas Hematology-Oncology Associates
Charlotte, North Carolina, United States, 28203
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle Cancer Care Alliance at Washington University
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Sarcoma Alliance for Research through Collaboration

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Brigitte C. Widemann, MD	National Cancer Institute (NCI)

More Information


Responsible Party:	Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier:	NCT00304083 History of Changes
Obsolete Identifiers:	NCT00266890
Other Study ID Numbers:	SARC006 SARC-006 NCI-06-C-0043 NCI-P6452 UMN-2007CG077
Study First Received:	March 15, 2006
Last Updated:	October 12, 2016

Keywords provided by Sarcoma Alliance for Research through Collaboration:


adult neurofibrosarcoma childhood neurofibrosarcoma metastatic childhood soft tissue sarcoma	nonmetastatic childhood soft tissue sarcoma stage IV adult soft tissue sarcoma neurofibromatosis type 1

Additional relevant MeSH terms:


Sarcoma Neurofibromatoses Neurofibroma Neurofibromatosis 1 Nerve Sheath Neoplasms Neurilemmoma Neurofibrosarcoma Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Neoplastic Syndromes, Hereditary Neurocutaneous Syndromes Nervous System Diseases Heredodegenerative Disorders, Nervous System	Neurodegenerative Diseases Genetic Diseases, Inborn Peripheral Nervous System Neoplasms Nervous System Neoplasms Peripheral Nervous System Diseases Neuromuscular Diseases Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neuroma Fibrosarcoma Neoplasms, Fibrous Tissue Neoplasms, Connective Tissue Doxorubicin Liposomal doxorubicin

ClinicalTrials.gov processed this record on August 16, 2017