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

• 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: Sarcoma Alliance for Research through Collaboration
• 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

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	NF1 MPNST	Sporadic MPNST
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

Baseline Characteristics

Arm/Group Title		NF1 MPNST	Sporadic MPNST	Total
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
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%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

37/48 patients total were evaluable for response.

Arm/Group Title	NF1 MPNST	Sporadic MPNST
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
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)

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

Analysis Population Description

The rows are among three different categories: Histologic Variant, Cellularity and Necrosis.

Arm/Group Title	NF1 MPNST	Sporadic MPNST
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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.
Description	Increase the knowledge of the epidemiology and clinical presentation of NF1-associated MPNSTs.
Time Frame	After 4 cycles

Outcome Measure Data

Analysis Population Description

Clinical evaluation of patients with NF1 was performed at trial enrollment.

Arm/Group Title		NF1 MPNST
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%

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	NF1 and Sporadic MPNST
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	--/--
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
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.

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Research Project Manager
• Organization: SARC
• Phone: 734-930-7600
• EMail: sarc@sarctrials.org

• 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