Neurofibromatosis Clinical Trials

• Males or females age ≥ 18 years who meet the NIH clinical criteria for the diagnosis of NF1

• Must have ≥8 measureable cNFs. Histologic confirmation of tumor is not necessary in the presence of consistent clinical findings or confirmed genetic testing. A Measurable cNF is defined as a cutaneous lesion that meets these criteria:

• Singular lesion surrounded by uninvolved skin measuring ≥ 5 mm in the longest diameter but not larger than 5 cm

∙ Not covered by hair

‣ There is no skin breakdown in the tumor or the skin around it

‣ Not located in an area that is prone to irritation or trauma.

‣ A tumor that has not received other therapies such as electrodessication, laser treatment, or prior resection or biopsy.

‣ Diffusely infiltrating cutaneous neurofibromas, subcutaneous neurofibromas, and plexiform neurofibromas are NOT eligible for treatment as photographic assessments and measurements with calipers or ruler are not possible or reliable.

‣ Participants must have 6 cNFs that are amenable for excision.

‣ Participants must be willing to undergo pre- and post-treatment tumor excisions providing fresh tumor tissue; there should be no contraindication for serial biopsies.

• Karnofsky performance level of ≥ 80%.

• Adequate organ and bone marrow and other organ function as defined by the following Screening laboratory values:

∙ Absolute neutrophil count ≥ 1,500 cells/µL;

‣ Platelets ≥ 100 x 103/µL;

‣ Hemoglobin ≥ 9.5 g/dL;

‣ Serum albumin ≥ 2.8 g/dL;

‣ Calculated creatinine clearance at Screening ≥ 60 mL/min (by Cockcroft-Gault formula) OR a normal serum creatinine.

‣ Alanine aminotransferase (ALT) ≤ 2x upper limit of institutional norm

‣ Total bilirubin value of ≤1.5 x Upper Limit of Normal (ULN) (isolated bilirubin ≥1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%)

• Participant is willing and able to comply with all aspects of the protocol

• Ability to understand and willingness to sign written informed consent document(s).

• Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding during any portion of the study and must use an adequate method to prevent pregnancy during the study period and for 3 months after treatment conclusion and agree not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of 3 months after last dose of study treatment. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment (see the Approved Methods of birth control listed below).

• For a woman to be determined not of childbearing potential, she must have ≥ 12 months of non-therapy-induced amenorrhea or be surgically or medically sterile.

• WOCBP must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test result at the Baseline visit prior to the first dose of study treatment if the Screening Day serum test was done more than 28 days prior.

• Male participants are eligible to participate if agreed to the following during the treatment period and for at least 90 days after the last dose of study treatment:

• \-- Refrain from donating sperm

• PLUS, either:

‣ Be abstinent from heterosexual intercourse and agree to remain abstinent until 90 days after the last study drug treatment; OR

⁃ Must agree to use a male condom when having sexual intercourse with a WOCBP and their female partner must utilize one the approved methods of birth control below:

• Approved Methods of birth control for this study are:

‣ Total abstinence

⁃ Male or female sterilization (vasectomy in males or surgical removal of ovaries or uterus in females)

⁃ Unsterilized male study participants must use a male condom, and their female partner must use one of the methods below:

⁃ Unsterilized female study participants must use one of the following highly effective methods listed below:

• Acceptable birth control methods which are considered highly effective if methods result in a failure rate of less than 1% per year when used consistently and correctly:

• Combined (estrogen and progestogen containing) hormonal contraceptive that stops the release of eggs from the ovary (oral, intravaginal, or transdermal)

• Progestogen-only hormonal contraception that stops the release of eggs from the ovary (oral, injectable, implantable)

• Intrauterine device (IUD)

• Intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion or bilateral tubal ligation