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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00304083
Recruitment Status : Completed
First Posted : March 17, 2006
Results First Posted : May 25, 2018
Last Update Posted : September 18, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sarcoma Alliance for Research through Collaboration

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neurofibromatosis Type 1
Sarcoma
Interventions Biological: filgrastim
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Procedure: conventional surgery
Radiation: radiation therapy
Enrollment 48
Recruitment Details  
Pre-assignment Details  
Arm/Group Title NF1 MPNST Sporadic MPNST
Hide Arm/Group Description

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Period Title: Overall Study
Started 34 14
Completed 4 Cycles 22 7
Patients Treated With Surgery 7 3
Patients Treated With Surgery and RT 5 1
Patients Treated With RT Only 4 2
Patients Had Neither RT or Surgery 6 1
Completed 12 6
Not Completed 22 8
Reason Not Completed
Withdrawal by Subject             4             2
Physician Decision             8             3
Disease Progression             5             1
Other             5             2
Arm/Group Title NF1 MPNST Sporadic MPNST Total
Hide Arm/Group Description

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Total of all reporting groups
Overall Number of Baseline Participants 34 14 48
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 34 participants 14 participants 48 participants
33
(8 to 66)
40
(13 to 72)
36.5
(8 to 72)
Sex/Gender, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants 14 participants 48 participants
Female
12
  35.3%
5
  35.7%
17
  35.4%
Male
22
  64.7%
9
  64.3%
31
  64.6%
1.Primary Outcome
Title Number of Participants With Response Rate (Complete Response and Partial Response)
Hide Description 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.
Time Frame After 4 Cycles (1 cycle=21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
37/48 patients total were evaluable for response.
Arm/Group Title NF1 MPNST Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 28 9
Measure Type: Count of Participants
Unit of Measure: Participants
Partial response
5
  17.9%
4
  44.4%
Complete response
0
   0.0%
0
   0.0%
Stable Disease
20
  71.4%
4
  44.4%
Progressive Disease
3
  10.7%
1
  11.1%
2.Secondary Outcome
Title Response of Plexiform Neurofibroma to Neoadjuvant Chemotherapy Using Volumetric MRI Analysis
Hide Description Evaluate the response of plexiformneurofibroma (if present) to neoadjuvant chemotherapy using WHO criteria and volumetric MRI analysis as a tool for response assessment
Time Frame After 4 Cycles (1 cycle=21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
MRI imaging of the MPNST and plexiform neurofibroma component was not sufficient to allow for volumetric analysis over time. Reasons include differences in imaging technique over time and incomplete coverage of the entire tumor.
Arm/Group Title NF1 MPNST Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Utility of Fludeoxyglucose F18 Positron Emission Tomography (18FDG-PET) and Automated MRI Volumetric Tumor Analysis to Assess Response to Treatment
Hide Description Evaluate the utility of fludeoxyglucose F18 positron emission tomography (18FDG-PET) and automated MRI volumetric tumor analysis as tools to assess response to treatment.
Time Frame After 4 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
This assessment involved 18FDG-PET and MRI imaging of the MPNST and plexiform neurofibroma component. Due to technical issues with MRI imaging, data was not reliably collected from any study participant to allow for meaningful analysis.
Arm/Group Title NF1 MPNST Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Response Evaluation Using WHO, RECIST, 18 FDG-PET and Volumetric MRI With Percent Necrosis in Tumor Specimens
Hide Description Correlate response evaluation using WHO, RECIST, 18 FDG-PET and volumetric MRI with percent necrosis in tumor specimens from patients who undergo surgery for local control after chemotherapy.
Time Frame After 4 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
33 patients were evaluable for response after cycle 4, response evaluation using WHO and RECIST was performed. Response evaluation was not assessed with 18 FDG-PET and volumetric MRI.
Arm/Group Title NF1 and Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 33
Measure Type: Count of Participants
Unit of Measure: Participants
Responses in agreement
29
  87.9%
Responses were not in agreement
4
  12.1%
5.Secondary Outcome
Title Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Hide Description 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.
Time Frame After 4 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
The rows are among three different categories: Histologic Variant, Cellularity and Necrosis.
Arm/Group Title NF1 MPNST Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 26 11
Measure Type: Count of Participants
Unit of Measure: Participants
Histologic Variant- Conventional
15
  57.7%
7
  63.6%
Histologic Variant- Perineural
1
   3.8%
0
   0.0%
Histologic Variant- Epithelioid
0
   0.0%
2
  18.2%
Histologic Variant- Divergent
1
   3.8%
0
   0.0%
Histologic Variant- Mixed histology
9
  34.6%
2
  18.2%
Low Cellularity
0
   0.0%
0
   0.0%
Moderate Cellularity
5
  19.2%
4
  36.4%
High Cellularity
21
  80.8%
7
  63.6%
Necrosis- absent
5
  19.2%
1
   9.1%
Necrosis 1-10%
8
  30.8%
2
  18.2%
Necrosis 10-50%
10
  38.5%
5
  45.5%
Necrosis >50%
3
  11.5%
3
  27.3%
6.Secondary Outcome
Title Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
Hide Description Construct a tissue microarray from submitted tumor samples that will be used in the future to identify novel targets for treatment of MPNSTs. The tissue microarray looked at various gene deletions and amplifications.
Time Frame After 4 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
The number of participants vary in the rows from overall number analyzed, due to the tissue that was available for testing.
Arm/Group Title NF1 MPNST Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 20 10
Measure Type: Number
Unit of Measure: participants
EGFR (7p12) amplification Number Analyzed 20 participants 8 participants
3 1
TOPO2A (17q21-q22) amplification Number Analyzed 19 participants 10 participants
5 2
Her2/Neu (17q11-q12) amplification Number Analyzed 18 participants 10 participants
2 0
Cyclin D1 (11q13) amplification Number Analyzed 19 participants 9 participants
1 2
c-MYC (8q24) amplification Number Analyzed 20 participants 8 participants
5 0
N-MYC (2p24) amplification Number Analyzed 16 participants 6 participants
3 1
NF1 (17q11) deletion Number Analyzed 19 participants 9 participants
7 0
p16 (9p21) deletion Number Analyzed 14 participants 6 participants
10 3
RB (13q14) deletion Number Analyzed 17 participants 10 participants
1 2
p53 (17q13) deletion Number Analyzed 19 participants 9 participants
6 2
7.Secondary Outcome
Title Identify the Number of Participants With a Serum Biomarker to Predict the Presence of MPNST Versus Benign Plexiform Neurofibroma
Hide Description Assess if a serum biomarker can be identified that predicts for the presence of a MPNST versus benign plexiform neurofibroma.
Time Frame After 4 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
Data looked at response evaluable patients with MPNST and focused on the TOPO2A gene being amplified.
Arm/Group Title NF1 and Sporadic MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
NF1 patients with gene amplified
3
  15.0%
Sporadic patients with gene amplified
2
  10.0%
8.Secondary Outcome
Title Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Hide Description Increase the knowledge of the epidemiology and clinical presentation of NF1-associated MPNSTs.
Time Frame After 4 cycles
Hide Outcome Measure Data
Hide Analysis Population Description
Clinical evaluation of patients with NF1 was performed at trial enrollment.
Arm/Group Title NF1 MPNST
Hide Arm/Group Description:

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

Overall Number of Participants Analyzed 34
Measure Type: Count of Participants
Unit of Measure: Participants
≥10 subcutaneous neurofibromas Number Analyzed 34 participants
10
  29.4%
6 or more CAL Number Analyzed 28 participants
17
  60.7%
Intertriginous freckling Number Analyzed 28 participants
19
  67.9%
Neurofibromas Number Analyzed 28 participants
26
  92.9%
Plexiform neurofibroma Number Analyzed 20 participants
12
  60.0%
Paraspinal neurofibromas Number Analyzed 24 participants
12
  50.0%
≥10 cutaneous neurofibromas Number Analyzed 24 participants
13
  54.2%
Optic glioma Number Analyzed 18 participants
1
   5.6%
Glioma Number Analyzed 18 participants
1
   5.6%
Scoliosis Number Analyzed 22 participants
5
  22.7%
Intellectual delay Number Analyzed 26 participants
8
  30.8%
Hypertension Number Analyzed 28 participants
8
  28.6%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NF1 and Sporadic MPNST
Hide Arm/Group Description

2 cycles of ifosfamide + doxorubicin ('IA') followed by 2 cycles of ifosfamide + etoposide ('IE') prior to local control measures (surgery and/or radiation therapy).

Local control with surgery and/or radiation will commence after recovery from toxicities. Patients, who undergo surgery only, will receive 2 more cycles of 'IA' followed by 2 cycles of 'IE' beginning after recovery from surgery. Patients, who receive radiation therapy in addition to surgery, will receive 2 cycles of 'IE' during radiation treatment, as doxorubicin cannot be concurrently administered with radiation therapy, and 2 cycles of 'IA' after completion of radiation treatment.

1 cycle = 21 days Doxo = Doxorubicin 37.5 mg/m2/dose IV over 15 minutes on days 1, 2 Ifos = Ifosfamide 1,800 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5 Etop = Etoposide 100 mg/m2/dose IV over 60 minutes on days 1, 2, 3, 4, 5

All-Cause Mortality
NF1 and Sporadic MPNST
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
NF1 and Sporadic MPNST
Affected / at Risk (%)
Total   13/48 (27.08%) 
Blood and lymphatic system disorders   
Febrile neutropenia   6/48 (12.50%) 
Anemia   4/48 (8.33%) 
Secondary acute myeloid leukemia   1/48 (2.08%) 
Nervous system disorders   
Somnolence   4/48 (8.33%) 
Psychiatric disorders   
Altered mental status   1/48 (2.08%) 
Aphasia   1/48 (2.08%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
NF1 and Sporadic MPNST
Affected / at Risk (%)
Total   3/48 (6.25%) 
Nervous system disorders   
Neurotoxicity  [1]  3/48 (6.25%) 
Indicates events were collected by systematic assessment
[1]
Eight patients had dose reductions of chemotherapy with three of those being for neurotoxicity associated with ifosfamide.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Research Project Manager
Organization: SARC
Phone: 734-930-7600
EMail: sarc@sarctrials.org
Layout table for additonal information
Responsible Party: Sarcoma Alliance for Research through Collaboration
ClinicalTrials.gov Identifier: NCT00304083    
Obsolete Identifiers: NCT00266890
Other Study ID Numbers: SARC006
SARC-006
NCI-06-C-0043
NCI-P6452
UMN-2007CG077
First Submitted: March 15, 2006
First Posted: March 17, 2006
Results First Submitted: April 16, 2018
Results First Posted: May 25, 2018
Last Update Posted: September 18, 2018