NeurofibromaPhase 1PDTNCT00716469
Phase I Clinical Study of the Safety of Photodynamic Therapy (PDT) Using LS11 in Children With Plexiform Neurofibromas
A Phase 1 study testing LS11 in people with Neurofibroma, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
Plexiform neurofibromas (PN) represent one of the most significant complications of NF1. They are a significant cause of morbidity in neurofibromatosis type 1 (NF1) by causing pain, impaired function, and disfigurement. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Neurofibroma
- What is being tested?
- LS11
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2008to Jul 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
- have a minimum dimension that is ≥ 5 cm in the plane of intended 25mm length Light Source insertion
- have a minimum dimension that is ≥ 3.15 cm perpendicular to the plane of intended 25mm length Light Source insertion
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- be accessible for percutaneous CT (and ultrasound if needed) guided Light Source insertion;
- 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.
- 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
- Renal: Serum creatinine within upper limit of institutional norm
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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
Plexiform neurofibromas (PN) represent one of the most significant complications of NF1. They are a significant cause of morbidity in neurofibromatosis type 1 (NF1) by causing pain, impaired function, and disfigurement. They may become life-threatening through mechanical compression of vital organs such as the trachea, great vessels, or spinal cord, and may significantly interfere with normal function when located in the extremities or orbit. The only effective therapy for PN is total surgical excision. However, due to local infiltration of normal tissue, gross total resection is usually not feasible, and often PN are completely unresectable due to their location, size, and multiplicity. To date, other therapeutic modalities, including radiotherapy and chemotherapy, have not shown efficacy in PN.
In the present study, local photodynamic therapy will be investigated. Photodynamic therapy (PDT) utilizes a drug, called a photosensitizer or photosensitizing agent, and a particular type of light. When photosensitizers are exposed to a specific wavelength of light, they produce a form of oxygen that kills nearby cells. PDT is expected to result in treatment response with shrinkage of tumor. The main purpose of the study is to determine the maximum amount of light that can be safely used with LS11 for PDT in children with plexiform neurofibromas.
Read the detailed description
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.
- Conditions
- Neurofibroma
- Being tested
- LS11
- Keywords
- Neurofibroma, Plexiform, NF1, Photo dynamic therapy
- Medical subject headings
- Neurofibroma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LS11Drug
Also called Talaporfin sodium
LS11 will be given as a one-time IV infusion over 3-5 minutes.
| Study group | Role | What they receive |
|---|---|---|
| LS11 Administration | Experimental | Treatment will be given with a standard 3+3 light dose escalation. The "Treatment Period" will be 28 days. The LS11 dose will be 30mg/m2. The initial light dose will be 50 J/cm. If criteria for dose escalation are met, then the light dose will be escalated to 100J/cm, 150J/cm and 200J/cm. Once the maximum light dose is determined, up to 6 additional patients will be treated at that level to gain further experience with this modality prior to phase II testing. In particular, at least 3 subjects <12 years of age will be enrolled at the maximum tolerable dose (MTD) to allow for further evaluation of safety in younger children. If grade 3 or 4 toxicities are noted at light dose level #1, the LS11 dose will be decreased to 20mg/m2 (2/3 of the standard dose). Receives: Drug: LS11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of photodynamic therapy (PDT) for the treatment of plexiform neurofibromas in children.
Measured: Week 4 and 12
Secondary outcomes (1)
To evaluate the change in quality of life of treated patients.
Measured: Week 4 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: The study is terminated due to expiration of study materials.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeurofibromaStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Michael Fisher, Children's Hospital of Philadelphia
- Investigators
- Michael J Fisher, M.D., Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00716469
- Sponsor's protocol ID
- 2006-10-5008
- Other IDs
- CHP-856 PDT
- Acronym
- PDT
- Status last verified
- Apr 2015
- First submitted
- 14 Jul 2008
- Last updated
- 15 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00716469
- Acronym / sponsor ID
- PDT / 2006-10-5008
- Conditions
- Neurofibroma
- Keywords
- Neurofibroma, Plexiform, NF1, Photo dynamic therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study is terminated due to expiration of study materials.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Jul 2008
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 16 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Plexiform neurofibromas (PN) represent one of the most significant complications of NF1. They are a significant cause of morbidity in neurofibromatosis type 1 (NF1) by causing pain, impaired function, and disfigurement. They may become life-threatening through mechanical compression of vital organs such as the trachea, great vessels, or spinal cord, and may significantly interfere with normal function when located in the extremities or orbit. The only effective therapy for PN is total surgical excision. However, due to local infiltration of normal tissue, gross total resection is usually not feasible, and often PN are completely unresectable due to their location, size, and multiplicity. To date, other therapeutic modalities, including radiotherapy and chemotherapy, have not shown efficacy in PN.
In the present study, local photodynamic therapy will be investigated. Photodynamic therapy (PDT) utilizes a drug, called a photosensitizer or photosensitizing agent, and a particular type of light. When photosensitizers are exposed to a specific wavelength of light, they produce a form of oxygen that kills nearby cells. PDT is expected to result in treatment response with shrinkage of tumor. The main purpose of the study is to determine the maximum amount of light that can be safely used with LS11 for PDT in children with plexiform neurofibromas.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LS11 Administration | Experimental | Drug: LS11Treatment will be given with a standard 3+3 light dose escalation. The "Treatment Period" will be 28 days. The LS11 dose will be 30mg/m2. The initial light dose will be 50 J/cm. If criteria for dose escalation are met, then the light dose will be escalated to 100J/cm, 150J/cm and 200J/cm. Once the maximum light dose is determined, up to 6 additional patients will be treated at that level to gain further experience with this modality prior to phase II testing. In particular, at least 3 subjects <12 years of age will be enrolled at the maximum tolerable dose (MTD) to allow for further evaluation of safety in younger children. If grade 3 or 4 toxicities are noted at light dose level #1, the LS11 dose will be decreased to 20mg/m2 (2/3 of the standard dose). |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (22 listed)
- 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:
- Minimum radial distance = 2.5 cm
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LS11Also: Talaporfin sodiumLS11 will be given as a one-time IV infusion over 3-5 minutes. | Drug | LS11 Administration |
Primary outcome
To determine the safety and tolerability of photodynamic therapy (PDT) for the treatment of plexiform neurofibromas in children.
Time frame: Week 4 and 12
1 secondary outcome
To evaluate the change in quality of life of treated patients.
Time frame: Week 4 and 12
Results and safety
The study was stopped early (reason given: The study is terminated due to expiration of study materials.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael J Fisher, M.D. principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LS11 in people with Neurofibroma, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study is terminated due to expiration of study materials.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the safety and tolerability of photodynamic therapy (PDT) for the treatment of plexiform neurofibromas in children. (time frame: Week 4 and 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2015.