Clinical trial NCT00862901: Safety Study Using Photodynamic Therapy Light Therapy for Patients With Chest Wall Progression of Breast Cancer and Satellite Metastases of Melanoma
Official title: A Phase I Trial of Continuous Low-Irradiance Photodynamic Therapy (CLIPT) for Patients Failing Radiation Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Skin Cancer
Keywords: cancer
skin metastases
chest wall progression of breast cancer
malignant melanoma
photodynamic therapy
photophrin
satellite and in-transit metastases of malignant melanoma
skin cancer
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
Collaborators: name: Susan G. Komen Breast Cancer Foundation
name: Axcan Pharma
First posted: 2009-03-17
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research is intended to explore a new approach to therapy when breast cancer recurs in the skin. The treatment, known as continuous low-irradiance photodynamic therapy, or CLIPT, has shown great promise in animal studies. The investigators goal is to evaluate CLIPT in people, using a novel light delivery system, to assess its side effects and the benefit it has in treating cancer. The investigators goal is to develop a safe, effective therapy that can be given in the doctor's office or possibly at home.

Detailed description: The goal of this research is to conduct a Phase I clinical study to assess the toxicity, safety and feasibility of a novel cancer treatment, Continuous Low Irradiance Photodynamic Therapy (CLIPT). This research will provide translation of recent promising preclinical work to human subjects with recurrent breast cancer.

BACKGROUND: Patients who develop post-mastectomy chest wall skin recurrence and fail conventional radiation therapy have few therapeutic options that can result in durable control. High-irradiance photodynamic therapy (PDT) has shown efficacy in patients with chest-wall progression of breast cancer that have failed radiation, surgery, and chemotherapy. However its clinical application has been severely limited as currently employed methods of PDT result in virtually 100% of patients develop skin necrosis, large areas of full-thickness ulceration, slow healing and chronic wound pain. In the rat and rabbit-brain tumor models, reducing the laser irradiance and increasing the exposure time to achieve a similar total fluence (fluence = irradiance x time) to standard PDT, avoids tissue necrosis while inducing apoptosis in the tumor but not normal tissue.

HYPOTHESIS: Low dose-rate (low irradiance) PDT may reduce or eliminate skin toxicity and enables treatment of skin/subcutaneous chest wall metastases in skin previously subjected to ionizing radiation.

SPECIFIC AIMS:

1) determine the fluence of CLIPT resulting in toxicity (maximum tolerated dose), defined as ulceration or necrosis of previously irradiated skin (non-tumor bearing skin within the prior ionizing radiation field) or normal skin, 2) evaluate the feasibility, ergonomics and safety of performing CLIPT via a proprietary electronically targetable fiber-optic "patch" placed directly on tumor-bearing, surrounding uninvolved previously irradiated skin and normal integument 3) study the tumor-bearing integument for clinical response to therapy by measuring complete, partial and no response to CLIPT.

STUDY DESIGN: We will perform a standard dose (laser fluence) escalation trial (holding drug level constant) in human subjects with post-mastectomy skin recurrences that have failed ionizing radiation therapy and assess toxicity in previously irradiated and normal integument.

POTENTIAL OUTCOMES \& BENEFITS: Therapeutic options for post-mastectomy cutaneous recurrences failing conventional radiotherapy are limited. If the pre-clinical results are replicated in human subjects, Phase II studies to evaluate CLIPT would be warranted. The long-term goal is to develop an unobtrusive, large-area CLIPT system in the form of a fiber-optically woven "garment" that can be worn by the patient outside the hospital setting for repeated and extended periods without causing skin breakdown or pain.

Eligibility criteria: Inclusion Criteria:

* Patients \> 18 years of age, with primary or metastatic cutaneous tumors that have been previously irradiated.
* Patients must have a target lesion and normal peri-umbilical skin that can be covered by the fiber-optic mesh used to deliver CLIPT (10 x 10 cm for Target lesion, and 1 x 1 cm for Control site).
* Patients must have a target lesion in a location other than the hands, feet, genitals, or face. Lesions in those locations will be excluded.
* Patients must sign informed consent.

Exclusion Criteria:

* Patients must not have received any systemic anti-cancer therapy within 30 days prior to enrolling in this study.
* Patients must not have received radiation therapy to the target site within 60 days of enrolling on this study.
* Patients with medical conditions associated with photosensitivity, such as cutaneous porphyria or a collagen vascular disease, or with known allergies to porphyrins will be excluded.
* Pregnant and nursing patients will be excluded. Women of child-bearing potential must have a negative serum or urine pregnancy test prior to enrollment.
* Patients taking medications known to cause photosensitivity (tetracyclines, sulfonamides, phenothiazines, sulfonylurea hypoglycemic agents, thiazide diuretics, griseofulvin, and fluoroquinolones) will be excluded.
* Laboratory values (Note: these are provided by the potential patient):
* Absolute neutrophil count \> 1000.
* Patients with severe hepatic dysfunction (total bilirubin, AST, or ALT \> five times upper limit of normal) will be excluded.
* Adequate coagulation status as indicated by platelet count \> 50,000, PT and PTT \< 1.5 time the upper limit of normal.
* Negative Urine or Serum Pregnancy Test

Note: No cost to patient, and no compensation provided.

Primary outcomes:
measure: Dose Limiting Toxicity (full thickness ulceration and/or necrosis of the skin)
timeFrame: 48 hours to 7 days after treatment
Secondary outcomes:
measure: Efficacy and mechanism of action of CLIPT.
timeFrame: 24 hours after treatment
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center, Department of Surgery
name: Roger Graham, MD
role: PRINCIPAL_INVESTIGATOR
References: