DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Overview | Consortium History | Management and Oversight | Research Site Details | Approved Trial Details

The Neurofibromatosis Clinical Trials Consortium (NFCTC, http://www.uab.edu/nfconsortium) was established by the Department of Defense Neurofibromatosis Research Program (NFRP) to develop and perform clinical trials for the treatment of neurofibromatosis (NF) complications in children and adults. The Consortium is composed of thirteen clinical sites, six collaborating sites, and an Operations Center at the University of Alabama at Birmingham under the direction of Dr. Bruce Korf. The purpose of the Operations Center is to provide administrative, data management, and statistical support to the NFCTC. Each of the clinical and collaborating sites has expertise in the treatment and management of NF and an established patient population available for clinical trials.

Approved NFCTC Clinical Trials (FY06 NFRP Award)

(1) STOPN: Sirolimus for the Treatment of NF1-Related Plexiform Neurofibromas
STOPN was a Phase II clinical trial to evaluate the mTOR inhibitor Sirolimus in the treatment of plexiform neurofibromas in children and adults with NF1. The goals of this trial were to find out if Sirolimus could stop or slow the growth of and/or shrink plexiform neurofibromas, evaluate the feasibility and toxicity of chronic Sirolimus administration, and characterize the active pharmacokinetic profile of Sirolimus when administered to this patient population. Enrollment was completed, and the study is closed. In the first stratum, the data indicated that Sirolimus can increase time to progression in NF1 patients with progressive plexiform neurofibromas. In the second stratum, the researchers observed that Sirolimus treatment did not lead to decreased tumor volume.

Status (March 2017): Study is closed.

ClinicalTrials.gov Identifier: NCT00634270

Publications:
Scott JR, Courter JD, Saldaña SN, et al. 2013. Population pharmacokinetics of sirolimus in pediatric patients with neurofibromatosis type 1. Therapeutic Drug Monitoring 35(3):332-337.
Weiss B, Widemann BC, Wolters P, et al. 2014. Sirolimus for non-progressive NF1-associated plexiform neurofibromas: An NF Clinical Trials Consortium Phase II study. Pediatr Blood Cancer. 2014 Jun;61(6):982-6.
Weiss B, Widemann BC, Wolters P, et al. 2015. Sirolimus for Progressive Neurofibromatosis Type 1-Associated Plexiform Neurofibromas: A Neurofibromatosis Clinical Trials Consortium Phase II Study. Neuro-Oncology, 2015 17(4):596-603.
Emoto C, Fukuda T, Mizuno T, et al. 2015. Age Dependent Changes in Sirolimus Metabolite Formation in Patients with Neurofibromatosis Type 1. Therapeutic Drug Monitoring, 2015 37(3):395-399.



(2) STARS: Lovastatin for the Treatment of Learning Disabilities in Children with NF1
STARS was a placebo-controlled, double-blind Phase II clinical trial to evaluate the effectiveness of Lovastatin™ in the treatment of learning disabilities in children with NF1. The goals of this study were to determine whether Lovastatin™ significantly improves visual spatial learning and/or sustained attention in children with NF1, affects measures of executive function, behavior, and quality of life in children with NF1 and cognitive deficits, and is safe and tolerable in this population. The study is closed. No improvement in the primary outcome measures was observed, but analysis of secondary outcome measures is still ongoing.

Status (March 2017): Ongoing, but enrollment is closed.

ClinicalTrials.gov Identifier: NCT00853580

(3) RAD001: RAD001 for Children with NF1 and Chemotherapy-Refractory Radiographic Progressive Low-Grade Gliomas
This is a single-arm Phase II trial to evaluate the effectiveness of RAD001 (or everolimus) in the treatment of pediatric patients with NF1 and low-grade gliomas (brain tumors and optic gliomas) that have not responded to standard therapies. In addition to evaluating the clinical response to RAD001, the safety of this drug was evaluated in this patient population. Enrollment is closed, and data from the study are currently being analyzed.

Status (March 2017): The RAD001 trial has met its enrollment goals and is currently in the data analysis phase.

ClinicalTrials.gov Identifier: NCT01158651

(4) RAD001 in Combination with Bevacizumab for Patients with Sporadic and NF1-Related Refractory MPNST
This Phase II clinical trial evaluated the use of RAD001 (everolimus) in combination with bevacizumab (Avastin) for patients with sporadic and NF1-related refractory MPNST. The primary goals of this trial were to evaluate the clinical benefit of treatment of chemotherapy refractory MPNST with RAD001 in combination with bevacizumab, and assess the toxicity and safety of this drug combination. The combination of everolimus and bevacizumab did not reach the study's target response rate and is not considered active in refractory malignant peripheral nerve sheath tumors. This study was being performed in collaboration with the Sarcoma Alliance for Research through Collaboration (SARC).

Status (March 2017): Study is closed.

ClinicalTrials.gov Identifier: NCT01661283

Approved NFCTC Clinical Trials (FY11 NFRP Award)

(1) Bevacizumab for NF2-Related Progressive Vestibular Schwannomas
This is an open-label, Phase II clinical trial to evaluate bevacizumab (Avastin) in children and young adults with NF2 and progressive vestibular schwannomas that are poor candidates for standard treatment with surgery or radiation. The primary objective of this study is to determine the hearing response rate after beginning treatment with bevacizumab for symptomatic vestibular schwannomas in children and young adults with NF2. The study is currently open for enrollment and ongoing.

Status (March 2017): Currently enrolling eligible participants.

ClinicalTrials.gov Identifier: NCT01767792

(2) Cabozantinib (XL184) for NF1-Related Plexiform Neurofibromas
This Phase II clinical trial will evaluate the response rate of adolescents and adults with NF1 and plexiform neurofibromas treated with Cabozantinib (XL184).

Status (March 2017): Initial enrollment is complete. The study is in follow-up and data analysis currently. Now that the pediatric dose of Cabozantinib has been identified, the study is being amended to add a separate stratum of 19 evaluable pediatric patients (<16 years of age).

ClinicalTrials.gov Identifier: NCT02101736

(3) PD-0325901 for NF1-Related Plexiform Neurofibromas
This Phase II clinical trial will evaluate the MEK inhibitor PD-0325901 for the treatment of NF1-related morbid plexiform neurofibromas in adolescents and adults. The primary endpoint is to determine whether treatment results in objective radiographic responses measured using MRI.

Status (March 2017): Enrollment is complete. The study is in follow-up and data analysis currently.

ClinicalTrials.gov Identifier: NCT02096471

(4) INFUSE Bone Graft for treatment of NF1-Related Tibial Pseudarthrosis (TPA)
This Phase II clinical trial will evaluate the utility of adding BMP-2 (INFUSE) at the surgical site of TPA repair in children and adolescents with NF1 with regard to improved bone healing. In addition to evaluating the clinical response to, the safety of this drug will be evaluated in a pediatric NF1 population.

Status (March 2017): Currently enrolling eligible participants.

ClinicalTrials.gov Identifier: NCT02718131

(5) Phase I/II Trial of Ganetespib in Combination with Sirolimus for Patients with Refractory MPNST
This Phase I/II trial will evaluate the use of the combination of ganetespib and sirolimus in patients with unresectable or metastatic sporadic or NF1 associated MPNST. The primary goals of this trial are to determine the dose and evaluate the safety and tolerability of the drug combination, as well as determine the clinical benefit in patients. This study is being performed in collaboration with SARC.

Status (March 2017): Ongoing, but enrollment is closed.

ClinicalTrials.gov Identifier: NCT02008877

(6) Phase I/II Study of MEK162 for Children with Low-Grade Gliomas and Other Ras/Raf/MAP Pathway Activated Tumors
This Phase I/II trial will evaluate the use of MEK162 in patients with low-grade gliomas, NF1 associated tumors, and other tumors thought to be caused by abnormal activation of the Ras/Raf/MEK molecular pathway. The primary goals of this trial are to determine the dose and evaluate the safety and tolerability of the treatment, as well as determine the clinical benefit in patients. The NFCTC sites are collaborating with non-consortium sites for the NF1-specific cohort in Phase II of the study.

Status (March 2017): Currently enrolling eligible participants.

ClinicalTrials.gov Identifier: NCT02285439

Last updated Thursday, May 18, 2017