Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors

NCT00304083 | Completed Phase 2 Results

• 5 other identifiers: SARC006SARC-006NCI-06-C-0043NCI-P6452UMN-2007CG077
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Neurofibromatosis Type 1; Sarcoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Response Rate (Complete Response and Partial Response)

  WHO criteria was used to determine responses due to the nonspherical shape of most MPNST. Complete Response (CR), Disappearance of all target lesions; Partial response (PR), \>=50% decrease of target lesions.

  After 4 Cycles (1 cycle=21 days)

Secondary Outcomes (7)

• Response of Plexiform Neurofibroma to Neoadjuvant Chemotherapy Using Volumetric MRI Analysis

  After 4 Cycles (1 cycle=21 days)

• Utility of Fludeoxyglucose F18 Positron Emission Tomography (18FDG-PET) and Automated MRI Volumetric Tumor Analysis to Assess Response to Treatment

  After 4 cycles

• Response Evaluation Using WHO, RECIST, 18 FDG-PET and Volumetric MRI With Percent Necrosis in Tumor Specimens

  After 4 cycles

• Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response

  After 4 cycles

• Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue

  After 4 cycles

Study Arms (2)

Chemotherapy and local control by radiotherapy and surgery

EXPERIMENTAL

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; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Procedure: conventional surgery; Radiation: radiation therapy

Chemotherapy and local control by surgery

EXPERIMENTAL

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; Drug: etoposide; Drug: ifosfamide; Procedure: conventional surgery

Interventions

filgrastim BIOLOGICAL

Given subcutaneously

Chemotherapy and local control by radiotherapy and surgery

doxorubicin hydrochloride DRUG

Given IV

Chemotherapy and local control by radiotherapy and surgery; Chemotherapy and local control by surgery

etoposide DRUG

Given IV

Chemotherapy and local control by radiotherapy and surgery; Chemotherapy and local control by surgery

ifosfamide DRUG

Given IV

Chemotherapy and local control by radiotherapy and surgery; Chemotherapy and local control by surgery

conventional surgery PROCEDURE

Patients undergo surgery

Chemotherapy and local control by radiotherapy and surgery; Chemotherapy and local control by surgery

radiation therapy RADIATION

Patients undergo radiotherapy

Chemotherapy and local control by radiotherapy and surgery

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• National Cancer Institute (NCI): collaborator

Study Sites (17)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University

Indianapolis, Indiana, 46202-5289, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0942, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Carolinas Hematology-Oncology Associates

Charlotte, North Carolina, 28203, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Oncology Hematology Associates

Philadelphia, Pennsylvania, 19106, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, 84112, United States

Location

Seattle Cancer Care Alliance at Washington University

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Neurofibromatosis 1; Sarcoma; Neurofibrosarcoma

Interventions

Filgrastim; Doxorubicin; Etoposide; Ifosfamide; Radiotherapy

Condition Hierarchy (Ancestors)

Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neoplasms, Connective and Soft Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Peripheral Nervous System Neoplasms; Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Results Point of Contact

• Title: Research Project Manager
• Organization: SARC

sarc@sarctrials.org

734-930-7600

Study Officials

• Brigitte C. Widemann, MD

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 17, 2006
• Study Start: December 1, 2005
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: September 18, 2018
• Results First Posted: May 25, 2018

Record last verified: 2018-05

Locations

US (17)