Trial Outcomes & Findings for Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors (NCT NCT00304083)
NCT ID: NCT00304083
Last Updated: 2018-09-18
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
48 participants
Primary outcome timeframe
After 4 Cycles (1 cycle=21 days)
Results posted on
2018-09-18
Participant Flow
Participant milestones
| Measure |
NF1 MPNST
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
|
Sporadic MPNST
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 Study
STARTED
|
34
|
14
|
|
Overall Study
Completed 4 Cycles
|
22
|
7
|
|
Overall Study
Patients Treated With Surgery
|
7
|
3
|
|
Overall Study
Patients Treated With Surgery and RT
|
5
|
1
|
|
Overall Study
Patients Treated With RT Only
|
4
|
2
|
|
Overall Study
Patients Had Neither RT or Surgery
|
6
|
1
|
|
Overall Study
COMPLETED
|
12
|
6
|
|
Overall Study
NOT COMPLETED
|
22
|
8
|
Reasons for withdrawal
| Measure |
NF1 MPNST
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
|
Sporadic MPNST
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 Study
Withdrawal by Subject
|
4
|
2
|
|
Overall Study
Physician Decision
|
8
|
3
|
|
Overall Study
Disease Progression
|
5
|
1
|
|
Overall Study
Other
|
5
|
2
|
Baseline Characteristics
Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors
Baseline characteristics by cohort
| Measure |
NF1 MPNST
n=34 Participants
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
|
Sporadic MPNST
n=14 Participants
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
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33 years
n=5 Participants
|
40 years
n=7 Participants
|
36.5 years
n=5 Participants
|
|
Sex/Gender, Customized
Female
|
12 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Sex/Gender, Customized
Male
|
22 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 4 Cycles (1 cycle=21 days)Population: 37/48 patients total were evaluable for 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.
Outcome measures
| Measure |
NF1 MPNST
n=28 Participants
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
|
Sporadic MPNST
n=9 Participants
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
|
|---|---|---|
|
Number of Participants With Response Rate (Complete Response and Partial Response)
Partial response
|
5 Participants
|
4 Participants
|
|
Number of Participants With Response Rate (Complete Response and Partial Response)
Complete response
|
0 Participants
|
0 Participants
|
|
Number of Participants With Response Rate (Complete Response and Partial Response)
Stable Disease
|
20 Participants
|
4 Participants
|
|
Number of Participants With Response Rate (Complete Response and Partial Response)
Progressive Disease
|
3 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: After 4 Cycles (1 cycle=21 days)Population: 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.
Evaluate the response of plexiformneurofibroma (if present) to neoadjuvant chemotherapy using WHO criteria and volumetric MRI analysis as a tool for response assessment
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After 4 cyclesPopulation: 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.
Evaluate the utility of fludeoxyglucose F18 positron emission tomography (18FDG-PET) and automated MRI volumetric tumor analysis as tools to assess response to treatment.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After 4 cyclesPopulation: 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.
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.
Outcome measures
| Measure |
NF1 MPNST
n=33 Participants
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
|
Sporadic MPNST
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
|
|---|---|---|
|
Response Evaluation Using WHO, RECIST, 18 FDG-PET and Volumetric MRI With Percent Necrosis in Tumor Specimens
Responses in agreement
|
29 Participants
|
—
|
|
Response Evaluation Using WHO, RECIST, 18 FDG-PET and Volumetric MRI With Percent Necrosis in Tumor Specimens
Responses were not in agreement
|
4 Participants
|
—
|
SECONDARY outcome
Timeframe: After 4 cyclesPopulation: The rows are among three different categories: Histologic Variant, Cellularity and Necrosis.
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.
Outcome measures
| Measure |
NF1 MPNST
n=26 Participants
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
|
Sporadic MPNST
n=11 Participants
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
|
|---|---|---|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Histologic Variant- Conventional
|
15 Participants
|
7 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Histologic Variant- Perineural
|
1 Participants
|
0 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Histologic Variant- Epithelioid
|
0 Participants
|
2 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Histologic Variant- Divergent
|
1 Participants
|
0 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Histologic Variant- Mixed histology
|
9 Participants
|
2 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Low Cellularity
|
0 Participants
|
0 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Moderate Cellularity
|
5 Participants
|
4 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
High Cellularity
|
21 Participants
|
7 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Necrosis- absent
|
5 Participants
|
1 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Necrosis 1-10%
|
8 Participants
|
2 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Necrosis 10-50%
|
10 Participants
|
5 Participants
|
|
Perform Pathologic Analysis of Tumor Samples to Analyze the Number of Participants With Markers as Predictors of Response
Necrosis >50%
|
3 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: After 4 cyclesPopulation: The number of participants vary in the rows from overall number analyzed, due to the tissue that was available for testing.
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.
Outcome measures
| Measure |
NF1 MPNST
n=20 Participants
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
|
Sporadic MPNST
n=10 Participants
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
|
|---|---|---|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
EGFR (7p12) amplification
|
3 participants
|
1 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
TOPO2A (17q21-q22) amplification
|
5 participants
|
2 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
Her2/Neu (17q11-q12) amplification
|
2 participants
|
0 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
Cyclin D1 (11q13) amplification
|
1 participants
|
2 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
c-MYC (8q24) amplification
|
5 participants
|
0 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
N-MYC (2p24) amplification
|
3 participants
|
1 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
NF1 (17q11) deletion
|
7 participants
|
0 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
p16 (9p21) deletion
|
10 participants
|
3 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
RB (13q14) deletion
|
1 participants
|
2 participants
|
|
Construct Tissue Microarray to Identify Novel Targets for Treatment for the Number of Participants With Available Tissue
p53 (17q13) deletion
|
6 participants
|
2 participants
|
SECONDARY outcome
Timeframe: After 4 cyclesPopulation: Data looked at response evaluable patients with MPNST and focused on the TOPO2A gene being amplified.
Assess if a serum biomarker can be identified that predicts for the presence of a MPNST versus benign plexiform neurofibroma.
Outcome measures
| Measure |
NF1 MPNST
n=20 Participants
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
|
Sporadic MPNST
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
|
|---|---|---|
|
Identify the Number of Participants With a Serum Biomarker to Predict the Presence of MPNST Versus Benign Plexiform Neurofibroma
NF1 patients with gene amplified
|
3 Participants
|
—
|
|
Identify the Number of Participants With a Serum Biomarker to Predict the Presence of MPNST Versus Benign Plexiform Neurofibroma
Sporadic patients with gene amplified
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: After 4 cyclesPopulation: Clinical evaluation of patients with NF1 was performed at trial enrollment.
Increase the knowledge of the epidemiology and clinical presentation of NF1-associated MPNSTs.
Outcome measures
| Measure |
NF1 MPNST
n=34 Participants
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
|
Sporadic MPNST
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
|
|---|---|---|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Plexiform neurofibroma
|
12 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Paraspinal neurofibromas
|
12 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
≥10 cutaneous neurofibromas
|
13 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Optic glioma
|
1 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Glioma
|
1 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Scoliosis
|
5 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Intellectual delay
|
8 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Hypertension
|
8 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
≥10 subcutaneous neurofibromas
|
10 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
6 or more CAL
|
17 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Intertriginous freckling
|
19 Participants
|
—
|
|
Provide Epidemiology and Clinical Presentation of the Number of Participants With NF1-associated MPNSTs.
Neurofibromas
|
26 Participants
|
—
|
Adverse Events
NF1 and Sporadic MPNST
Serious events: 13 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
NF1 and Sporadic MPNST
n=48 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
12.5%
6/48
|
|
Blood and lymphatic system disorders
Anemia
|
8.3%
4/48
|
|
Psychiatric disorders
Altered mental status
|
2.1%
1/48
|
|
Psychiatric disorders
Aphasia
|
2.1%
1/48
|
|
Nervous system disorders
Somnolence
|
8.3%
4/48
|
|
Blood and lymphatic system disorders
Secondary acute myeloid leukemia
|
2.1%
1/48
|
Other adverse events
| Measure |
NF1 and Sporadic MPNST
n=48 participants at risk
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
|
|---|---|
|
Nervous system disorders
Neurotoxicity
|
6.2%
3/48
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place