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Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T (DCLNF1)

Primary Purpose

Neurofibromatosis 1

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Everolimus
Sponsored by
The University of Texas Health Science Center, Houston
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neurofibromatosis 1 focused on measuring Neurofibroma, NF-1, Everolimus, mTOR inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient is at least 18 years of age at the time of enrollment
  2. Informed consent
  3. Compliance with trial requirements (photography, lab draws, medication schedules, and study visits)
  4. Diagnosis of NF 1 and has cutaneous neurofibromas that are located in in a region amenable to photography
  5. Females of child bearing potential must not be pregnant as confirmed by a negative pregnancy test (blood beta-hCG level) prior to study enrollment and must agree to use appropriate contraceptive methods for the duration of the trial
  6. Patient must have adequate liver function as shown by, total bilirubin </= 2.0 mg/dL, ALT and AST </= 2.5 X ULN, INR </= 2

8. Patient must have adequate renal function, serum creatinine </= 1.5 X ULN 9. Patient must have adequate lipid profile, fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L, fasting triglycerides </= X ULN

Exclusion Criteria:

1. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.) 2. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) 3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus 4. Uncontrolled diabetes mellitus despite adequate therapy 5. Patients who have any severe and /or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction </= prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease, symptomatic congestive heart failure of New York Hear Association Class III or IV, known active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, or chronic hepatitis, known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), active, bleeding diathesis, chronic treatment with corticosteroids, or other immunosuppressive agents, topical or inhaled corticosteroids are allowed, know history of HIV seropositivity, patients who have received live attenuated vaccines within 1 week of start of Everolimus. Patient would avoid close contact with others who have received live attenuated vaccines during the study, patients who have a history of primary malignancy, with the exceptions of mon-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for >/- 3 years, patients with a history of non compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study, patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing, pregnant or nursing (lactating) women, women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. highly effective contraception methods,male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment.

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Sites / Locations

  • The University of Texas Health Science Center at Houston

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention

Arm Description

This is a single arm intervention using Everolimus

Outcomes

Primary Outcome Measures

3D Photographic Measurement of Surface Volume
Photographs of selected lesions to measure surface volume.

Secondary Outcome Measures

Number of Participants With Grade 3-4 Adverse Events
Determination if orally administered Afinitor is safe in patients a indicated by lack of Grade 3-4 adverse events during the trial period.

Full Information

First Posted
December 12, 2014
Last Updated
May 16, 2017
Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Texas Neurofibromatosis Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02332902
Brief Title
Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T
Acronym
DCLNF1
Official Title
Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1- CRAD001CUS232T
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
February 2015 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
Collaborators
Texas Neurofibromatosis Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This trial is evaluating the use of oral Everolimus to determine if there is a reduction in the size of the disfiguring cutaneous lesions in patients with Neurofibromatosis 1 over a 6 month period. The evaluation will be done by 3D photography measuring volume with the LIFEVIZ Micro system.
Detailed Description
Qualifying subjects will have a diagnosis of Neurofibromatosis 1 and have disfiguring cutaneous lesions that can be measured by photography. The subjects will have photographs of the target lesions,biopsies of the lesions,and safety blood laboratory tests at 3 time points (baseline, 3 months and 6 months which is end of treatment). Everolimus will be taken orally for 6 months. Subjects will visit the clinic monthly for an exam and adverse event evaluation. Laboratory testing will be done at these visits if determined necessary by the PI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurofibromatosis 1
Keywords
Neurofibroma, NF-1, Everolimus, mTOR inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Experimental
Arm Description
This is a single arm intervention using Everolimus
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
Afinitor
Intervention Description
Everyone in the study will receive Everolimus at a starting dose of 10 mg daily and will be adjusted up or down by 2.5 mg at 2 week intervals to attain a trough concentration of 5-15 ng/ml
Primary Outcome Measure Information:
Title
3D Photographic Measurement of Surface Volume
Description
Photographs of selected lesions to measure surface volume.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Number of Participants With Grade 3-4 Adverse Events
Description
Determination if orally administered Afinitor is safe in patients a indicated by lack of Grade 3-4 adverse events during the trial period.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Determine How Orally Administered Everolimus Effects mTOR Signaling in NF-1 Tissues
Description
Quantification via immunohistochemical staining of PTEN, pS6, p4EBP-1, TSC2, mTOR, NF-1, pAKT, VEGF-A and IGF-IR expression in biopsied neurofibroma tissue samples.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient is at least 18 years of age at the time of enrollment Informed consent Compliance with trial requirements (photography, lab draws, medication schedules, and study visits) Diagnosis of NF 1 and has cutaneous neurofibromas that are located in in a region amenable to photography Females of child bearing potential must not be pregnant as confirmed by a negative pregnancy test (blood beta-hCG level) prior to study enrollment and must agree to use appropriate contraceptive methods for the duration of the trial Patient must have adequate liver function as shown by, total bilirubin </= 2.0 mg/dL, ALT and AST </= 2.5 X ULN, INR </= 2 8. Patient must have adequate renal function, serum creatinine </= 1.5 X ULN 9. Patient must have adequate lipid profile, fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L, fasting triglycerides </= X ULN Exclusion Criteria: 1. Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.) 2. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus) 3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus 4. Uncontrolled diabetes mellitus despite adequate therapy 5. Patients who have any severe and /or uncontrolled medical conditions such as: unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction </= prior to start of Everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease, symptomatic congestive heart failure of New York Hear Association Class III or IV, known active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, or chronic hepatitis, known severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air), active, bleeding diathesis, chronic treatment with corticosteroids, or other immunosuppressive agents, topical or inhaled corticosteroids are allowed, know history of HIV seropositivity, patients who have received live attenuated vaccines within 1 week of start of Everolimus. Patient would avoid close contact with others who have received live attenuated vaccines during the study, patients who have a history of primary malignancy, with the exceptions of mon-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for >/- 3 years, patients with a history of non compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study, patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing, pregnant or nursing (lactating) women, women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing of study treatment. highly effective contraception methods,male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment. -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Kay Koenig, MD
Organizational Affiliation
The University of Texas Health Science Center, Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30284154
Citation
Slopis JM, Arevalo O, Bell CS, Hebert AA, Northrup H, Riascos RF, Samuels JA, Smith KC, Tate P, Koenig MK. Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis-1 with Everolimus: A Phase II, Open-Label, Single-Arm Trial. Drugs R D. 2018 Dec;18(4):295-302. doi: 10.1007/s40268-018-0248-6.
Results Reference
derived

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Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T

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