CHP-856: Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using Intratumoral Delivery of Non-coherent Light for Photoactivation of LS11 in Children With Plexiform Neurofibromas
3 Years
21 Years
Both
Neurofibroma
Trial Information
CHP-856: Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using Intratumoral Delivery of Non-coherent Light for Photoactivation of LS11 in Children With Plexiform Neurofibromas
Current treatment options for PN are limited. The only effective therapy for PN is complete
surgical resection. Incompletely resected lesions have a high incidence of recurrence, often
resulting in the necessity of several surgeries over a patient's lifetime. Development of
non-surgical treatments for PN is a high priority. To date, other therapeutic modalities,
including radiotherapy and chemotherapy, have not shown efficacy in PN, although it is
arguable that these modalities have not been sufficiently studied. Newer approaches,
including anti-angiogenesis agents, farnesyl transferase inhibitors, and inhibitors of
growth factor pathways are in development and are being studied, but are clearly not proven
therapies.
Investigational Agent LS11, talaporfin sodium, was specifically developed as a
photosensitizing agent for use in photodynamic therapy. The light activation of LS11 leads
to the formation of singlet oxygen causing damage to the vascular endothelial cells leading
to vascular thrombosis and occlusion.
Phase I and II studies were conducted in the US and Japan using LS11. PDT with LS11 was
generally well tolerated in these studies and there were no serious adverse events noted.
PDT is a novel treatment modality in which a systemically administered photosensitizer (LS11
in our proposal) is activated locally by illuminating the diseased tissue with light of a
specific wavelength. Light activation of LS11 leads to the formation of reactive oxygen
species that cause damage to the vascular endothelial cells leading to vascular thrombosis
and occlusion and subsequently death of tumor cells.
Light Source Placement: Ultrasound may be used to monitor the percutaneous implantation of
the Light Source. However, the position of the implanted Light Source must be verified by
computed tomography (CT).
- Use a RITA introducer that has a trochar.
- Make a small incision in the skin.
- Insert the introducer into the tumor and advance to the desired position in the target
tissue (using ultrasound or CT to verify placement).
- Remove the trochar.
- Insert the Light Source catheter to the end of the sheath. (Avoid mechanical damage to
the device, such as twisting, kinking, or exerting force during insertion).
- Pull the sheath back at least 4 centimeters (cm) (the Light Source has to remain in
position and not be pulled back with the sheath).
- Verify the Light Source tip location by CT. Reposition if necessary.
- The sheath may be removed completely, after verifying Light Source tip location, at the
physician's discretion
- Record distance to lesion surface and to vital structures of the implanted light
source.
- Secure the Light Source
LS11 Administration:
- Since compatibility between LS11 and other drugs is not established, LS11 should not be
mixed with or physically added to other drugs.
- Every effort should be made to avoid extravasation of LS11 in the surrounding tissue.
The extravasated drug may pose prolonged photosensitivity risk to the tissue near the
injection site.
- To avoid extravasation, establish an intravenous (IV) line and ensure that there is a
free flow of saline or dextrose and water. If a heparin lock is used, flush thoroughly
with saline.
- LS11 should be slowly (over 3-5 minutes) administered intravenously as a single dose of
30 mg/m2 or 40 mg/m2.
- Following the injection the line should be flushed with at least 10 cc of saline or
dextrose and water.
- In case of extravasation, the site should be thoroughly rinsed with saline or water and
carefully bandaged to protect the area from room- and sun-light. The photosensitivity
at the extravasated site will last longer than general cutaneous photosensitivity.
- Record the administration start time and end time.
Physical exam, blood tests, electrocardiogram (ECG) and magnetic resonance imaging (MRI)
will be performed prior to starting on study and regularly after the treatment per protocol.
Light Exposure Precautions Following PDT-Instructions for Patients: Patients will be
sensitive to light and must observe precautions to reduce exposure of skin and eyes to
direct sunlight and bright indoor lighting for up to 14 days. The sensitivity to light is
due to residual drug that will be present in all parts of the skin and eyes. To minimize
skin reactions due to light exposure after LS11 administration, precautions should be taken
as detailed in the protocol.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the safety and tolerability of photodynamic therapy (PDT) for the treatment of plexiform neurofibromas in children.
Outcome Time Frame:
Week 4 and 12
Safety Issue:
Yes
Principal Investigator
Michael J Fisher, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Hospital of Philadelphia
Authority:
United States: Food and Drug Administration
Study ID:
CHP-856 PDT
NCT ID:
NCT00716469
Start Date:
July 2008
Completion Date:
July 2012
Related Keywords:
- Neurofibroma
- Neurofibroma
- Plexiform
- NF1
- Photo dynamic therapy
- Neurofibroma
- Neurofibroma, Plexiform
Name | Location |
|---|---|
| The Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
