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

NCT00716469 | Terminated Phase 1 DMC

• 2 other identifiers: 2006-10-5008CHP-856 PDT
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Neurofibroma

Keywords

Neurofibroma; Plexiform; NF1; Photo dynamic therapy

Outcome Measures

Primary Outcomes (1)

• To determine the safety and tolerability of photodynamic therapy (PDT) for the treatment of plexiform neurofibromas in children.

  Week 4 and 12

Secondary Outcomes (1)

• To evaluate the change in quality of life of treated patients.

  Week 4 and 12

Study Arms (1)

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).

Drug: LS11

Interventions

LS11 DRUG

LS11 will be given as a one-time IV infusion over 3-5 minutes.

Also known as: Talaporfin sodium

LS11 Administration

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• United States Department of Defense: collaborator

Study Sites (1)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Neurofibroma

Interventions

Talaporfin

Condition Hierarchy (Ancestors)

Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Peripheral Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Officials

• Michael J Fisher, M.D.

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof.

Study Record Dates

• First Submitted: July 14, 2008
• First Posted: July 16, 2008
• Study Start: July 1, 2008
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: April 15, 2015

Record last verified: 2015-04

Locations

US (1)