Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using LS11 in Children With Plexiform Neurofibromas

Inclusion Criteria:

• Age: Patients must be ≥ 3 and ≤ 21 years of age.
• Tumor: Patients must have a debilitating, severely disfiguring, life-threatening, or progressive plexiform neurofibroma (PN), which is not surgically resectable and for which there is no other standard medical management.
• Measurable Disease: Patients must have a measurable PN assessed by MRI within 2 weeks prior to starting therapy.

• Tumor Size/Shape/Location:All tumors must:

  1. have a minimum dimension that is ≥ 5 cm in the plane of intended 25mm length Light Source insertion
  2. have a minimum dimension that is ≥ 3.15 cm perpendicular to the plane of intended 25mm length Light Source insertion
  3. be accessible for percutaneous CT (and ultrasound if needed) guided Light Source insertion;
  4. have a shape and location such that the minimum distance between the Light Source and any "critical structure" (defined in section 4.3.4) will be as follows:
• Minimum radial distance = 2.5 cm
• Minimum distance from proximal end of Light Source = 2.5 cm
• Minimum distance from distal end of Light Source = 2 cm
• For patients with NF1: In addition to PN, all study subjects must have at least one other diagnostic criteria for NF1.
• Performance Status: Patients should have a life expectancy of at least 6 months and a Karnofsky (≥ 16 years of age) or Lansky (≤16 years of age) Performance Score ≥ 60.
• Prior/Concurrent Therapy: Patients must have recovered from any specific acute toxicity associated with prior therapy. No concurrent anti-tumor therapy is allowed.

• Laboratory: Patients must have adequate bone marrow, renal, and hepatic function assessed within 7 days prior to start of therapy.

  1. Hematologic:

     Absolute neutrophil count ≥ 1000/ul Platelet count ≥ 100,000/ul Hemoglobin ≥ 8 g/dL PT/PTT ≤ 1.2 times institutional upper limit of normal

  2. Renal: Serum creatinine within upper limit of institutional norm
  3. Hepatic:

Bilirubin ≤ 1.5 times upper limit of normal for age ALT ≤ 2.5 times institutional upper limit of normal for age Albumin ≥ 2 g/dL

• Pregnancy: Female patients of childbearing potential must have negative serum or urine pregnancy test. Patient must not be pregnant or breast-feeding. Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
• Informed Consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an IRB approved document of informed consent indicating their understanding of the investigational nature and the risks of this study before beginning therapy. When appropriate, pediatric patients will be included in all discussions in order to obtain verbal assent.

Exclusion Criteria:

• Patients < 3 or > 21 years of age.
• Tumors that are not debilitating, severely disfiguring, life-threatening, or progressive
• Patients with baseline pain or neuropathy related to their target lesion that is so severe that it effects activities of daily living (i.e. grade 3 or 4).
• Tumors that would require Light Source placement such that a "critical structure" is within the minimum distance required between a "critical structure" and Light Source.
• Tumor that is inaccessible for percutaneous implantation of light source by interventional radiology.
• Patients with a history of porphyria.
• Concomitant use of other drugs known to produce skin photosensitivity (e.g. tetracyclines, sulfonamides, phenothiazines, sulfonylureas, thiazide diuretics, and griseofulvin)
• Patients with any serious medical illnesses that, in the investigator's opinion, would compromise a patient's ability to tolerate this therapy.
• Patients receiving any other chemotherapeutics or investigational agents.
• Patients with uncontrolled infections.
• Patients taking NSAIDs or anti-coagulants.