SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

Christine S. Higham; Seth M. Steinberg; Eva Dombi; Arie Perry; Lee J. Helman; Scott M. Schuetze; Joseph A. Ludwig; Arthur Staddon; Mohammed M. Milhem; Daniel Rushing; Robin L. Jones; Michael Livingston; Stewart Goldman; Christopher Moertel; Lars Wagner; David Janhofer; Christina M. Annunziata; Denise Reinke; Lauren Long; David Viskochil; Larry Baker; Brigitte C. Widemann

doi:10.1155/2017/8685638

SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

Christine S. Higham, Seth M. Steinberg, Eva Dombi, Arie Perry, Lee J. Helman, Scott M. Schuetze, Joseph A. Ludwig, Arthur Staddon, Mohammed M. Milhem, Daniel Rushing, Robin L. Jones, Michael Livingston, Stewart Goldman, Christopher Moertel, Lars Wagner, David Janhofer, Christina M. Annunziata, Denise Reinke, Lauren Long, David ViskochilLarry Baker, Brigitte C. Widemann

Pediatric Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

Abstract

Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

Original language	English (US)
Article number	8685638
Journal	Sarcoma
Volume	2017
DOIs	https://doi.org/10.1155/2017/8685638
State	Published - 2017

Bibliographical note

Funding Information:
2.1. Study Oversight. This multi-institutional trial was sponsored by the United States Department of Defense (DoD), developed by NCI investigators in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC) and coordinated by SARC. The protocol was approved by the local institutional review board at each participating site and registered on ClinicalTrials.gov NCT00304083. All patients or their legal guardians provided written informed consent and assent (patients 13 through 17 years old).

Funding Information:
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Department of Defense Neurofibromatosis Research Program under Award no. W81XWH-06-1-0434. This research was also supported, in part, through the NCI CCR Intramural Research Program.

Publisher Copyright:
© 2017 Christine S. Higham et al.

Publisher link

10.1155/2017/8685638

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613633

Find It

Find It at U of M Libraries

Cite this

Higham, C. S., Steinberg, S. M., Dombi, E., Perry, A., Helman, L. J., Schuetze, S. M., Ludwig, J. A., Staddon, A., Milhem, M. M., Rushing, D., Jones, R. L., Livingston, M., Goldman, S., Moertel, C., Wagner, L., Janhofer, D., Annunziata, C. M., Reinke, D., Long, L., ... Widemann, B. C. (2017). SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors. Sarcoma, 2017, [8685638]. https://doi.org/10.1155/2017/8685638

Higham, CS, Steinberg, SM, Dombi, E, Perry, A, Helman, LJ, Schuetze, SM, Ludwig, JA, Staddon, A, Milhem, MM, Rushing, D, Jones, RL, Livingston, M, Goldman, S, Moertel, C, Wagner, L, Janhofer, D, Annunziata, CM, Reinke, D, Long, L, Viskochil, D, Baker, L & Widemann, BC 2017, 'SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors', Sarcoma, vol. 2017, 8685638. https://doi.org/10.1155/2017/8685638

@article{093218da9ff34cf9ac1c0e97e2861230,

title = "SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors",

abstract = "Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.",

author = "Higham, {Christine S.} and Steinberg, {Seth M.} and Eva Dombi and Arie Perry and Helman, {Lee J.} and Schuetze, {Scott M.} and Ludwig, {Joseph A.} and Arthur Staddon and Milhem, {Mohammed M.} and Daniel Rushing and Jones, {Robin L.} and Michael Livingston and Stewart Goldman and Christopher Moertel and Lars Wagner and David Janhofer and Annunziata, {Christina M.} and Denise Reinke and Lauren Long and David Viskochil and Larry Baker and Widemann, {Brigitte C.}",

note = "Funding Information: 2.1. Study Oversight. This multi-institutional trial was sponsored by the United States Department of Defense (DoD), developed by NCI investigators in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC) and coordinated by SARC. The protocol was approved by the local institutional review board at each participating site and registered on ClinicalTrials.gov NCT00304083. All patients or their legal guardians provided written informed consent and assent (patients 13 through 17 years old). Funding Information: This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Department of Defense Neurofibromatosis Research Program under Award no. W81XWH-06-1-0434. This research was also supported, in part, through the NCI CCR Intramural Research Program. Publisher Copyright: {\textcopyright} 2017 Christine S. Higham et al.",

year = "2017",

doi = "10.1155/2017/8685638",

language = "English (US)",

volume = "2017",

journal = "Sarcoma",

issn = "1357-714X",

publisher = "Hindawi Publishing Corporation",

}

TY - JOUR

T1 - SARC006

T2 - Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

AU - Higham, Christine S.

AU - Steinberg, Seth M.

AU - Dombi, Eva

AU - Perry, Arie

AU - Helman, Lee J.

AU - Schuetze, Scott M.

AU - Ludwig, Joseph A.

AU - Staddon, Arthur

AU - Milhem, Mohammed M.

AU - Rushing, Daniel

AU - Jones, Robin L.

AU - Livingston, Michael

AU - Goldman, Stewart

AU - Moertel, Christopher

AU - Wagner, Lars

AU - Janhofer, David

AU - Annunziata, Christina M.

AU - Reinke, Denise

AU - Long, Lauren

AU - Viskochil, David

AU - Baker, Larry

AU - Widemann, Brigitte C.

N1 - Funding Information: 2.1. Study Oversight. This multi-institutional trial was sponsored by the United States Department of Defense (DoD), developed by NCI investigators in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC) and coordinated by SARC. The protocol was approved by the local institutional review board at each participating site and registered on ClinicalTrials.gov NCT00304083. All patients or their legal guardians provided written informed consent and assent (patients 13 through 17 years old). Funding Information: This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Department of Defense Neurofibromatosis Research Program under Award no. W81XWH-06-1-0434. This research was also supported, in part, through the NCI CCR Intramural Research Program. Publisher Copyright: © 2017 Christine S. Higham et al.

PY - 2017

Y1 - 2017

N2 - Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

AB - Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

UR - http://www.scopus.com/inward/record.url?scp=85030625813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030625813&partnerID=8YFLogxK

U2 - 10.1155/2017/8685638

DO - 10.1155/2017/8685638

M3 - Article

C2 - 29138631

AN - SCOPUS:85030625813

SN - 1357-714X

VL - 2017

JO - Sarcoma

JF - Sarcoma

M1 - 8685638

ER -

SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

Abstract

Bibliographical note

Publisher link

Find It

Other files and links

Fingerprint

Cite this