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Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Malignant Peripheral Nerve Sheath Tumors


Phase 2
N/A
N/A
Open (Enrolling)
Both
Neurofibromatosis Type 1, Sarcoma

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Trial Information

Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Malignant Peripheral Nerve Sheath Tumors


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (complete response and partial response)

Safety Issue:

No

Principal Investigator

Brigitte C. Widemann, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Food and Drug Administration

Study ID:

SARC006

NCT ID:

NCT00304083

Start Date:

December 2005

Completion Date:

Related Keywords:

  • Neurofibromatosis Type 1
  • Sarcoma
  • adult neurofibrosarcoma
  • childhood neurofibrosarcoma
  • metastatic childhood soft tissue sarcoma
  • nonmetastatic childhood soft tissue sarcoma
  • stage IV adult soft tissue sarcoma
  • neurofibromatosis type 1
  • Neurofibromatoses
  • Neurofibromatosis 1
  • Osteitis Fibrosa Cystica
  • Nerve Sheath Neoplasms
  • Neurofibrosarcoma
  • Neurilemmoma
  • Sarcoma

Name

Location

University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Carolinas Hematology-Oncology AssociatesCharlotte, North Carolina  28203
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
M. D. Anderson Cancer Center at University of TexasHouston, Texas  77030-4009
Huntsman Cancer Institute at University of UtahSalt Lake City, Utah  84112
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
University of MinnesotaMinneapolis, Minnesota  55455
Pennsylvania Oncology Hematology AssociatesPhiladelphia, Pennsylvania  19107
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182
Indiana UniversityIndianapolis, Indiana  46202
Johns HopkinsBaltimore, Maryland  21231
Sarcoma Oncology CenterSanta Monica, California  90403
Seattle Cancer Care Alliance at Washington UniversitySeattle, Washington  98109