Photodynamic Therapy Using Lutetium Texaphyrin in Treating Patients With Cervical Intraepithelial Neoplasia

Phase I Study Photodynamic Therapy Using Lutrin (Lutetium Texaphyrin) in the Treatment of Patients With Cervical Intraepithelial Neoplasia

Patrocinadores

Patrocinador principal: National Cancer Institute (NCI)

Fuente National Cancer Institute (NCI)
Resumen breve

Phase I trial to study the effectiveness of photodynamic therapy with lutetium texaphyrin in treating patients who have cervical intraepithelial neoplasia. Photodynamic therapy uses light and drugs such as lutetium texaphyrin that make abnormal cells more sensitive to light and may kill abnormal cells in the cervix and prevent the development of cervical cancer

Descripción detallada

OBJECTIVES:

I. Determine the optimal dosage with the least toxicity of lutetium texaphyrin as well as the length of time following its systemic injection that provides the maximum differential in drug uptake between the target dysplastic squamous cells and normal squamous epithelium when given to patients with cervical intraepithelial neoplasia (CIN).

II. Determine, by histomorphometry, the photodynamic light dose that demonstrates the greatest treatment selectivity between normal cervical epithelium and CIN with the least amount of cervical pain and necrosis.

OUTLINE: This is a dose-escalation study of lutetium texaphyrin (part 1) followed by a dose-escalation study of light fluence (part 2).

Part 1: Patients receive lutetium texaphyrin IV over 5-20 minutes. Patients undergo in vivo tissue assessment by spectrometer at 0, 1, 3, 5, 12, and 24 hours and loop electrical excision procedure (LEEP) at 24 hours after lutetium texaphyrin infusion.

Part 2: Patients receive lutetium texaphyrin IV over 5-20 minutes. A laser delivers 730 nm of light to the cervix for 4, 8, or 16 minutes. Patients undergo LEEP at 4, 8, or 12 hours after exposure of the cervix to the light source.

Cohorts of 9 patients receive escalating doses of lutetium texaphyrin (part 1) and then light fluence (part 2) until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which 2 of 9 patients experience dose-limiting toxicity.

Patients are followed at 48 hours, weekly for 1 month, and then at 4 months.

PROJECTED ACCRUAL: A maximum of 54 patients will be accrued for this study.

Estado general Terminated
Fecha de inicio December 2000
Fecha de finalización primaria April 2004
Fase Phase 1
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1) Up to 24 hours
Maximal differential in Lutrin tissue levels between normal and dysplastic cells (Part 1) At the time of LEEP
Percentage of tissue demonstrating PDT related effects (apoptosis/ necrosis) for normal versus abnormal epithelium at each total fluence for each LEEP cone biopsy specimen At LEEP time
Inscripción 54
Condición
Intervención

Tipo de intervención: Drug

Nombre de intervención: motexafin lutetium

Descripción: Given IV

Tipo de intervención: Drug

Nombre de intervención: photodynamic therapy

Descripción: Undergo laser therapy

Etiqueta de grupo de brazo: Part 2 (lutetium texaphyrin, laser therapy, LEEP)

Tipo de intervención: Procedure

Nombre de intervención: loop electrosurgical excision procedure

Descripción: Undergo LEEP

Tipo de intervención: Other

Nombre de intervención: laboratory biomarker analysis

Descripción: Correlative studies

Elegibilidad

Criterios:

Inclusion Criteria:

- Cervical intraepithelial neoplasia (CIN) grade II or III

- No cytologic, colposcopic, or histologic evidence of invasive squamous cell carcinoma

- No evidence of glandular atypia on Pap smear, endocervical curettage, or biopsy

- No inadequate colposcopy (i.e., entire transformation zone cannot be visualized and/or upper limit of a colposcopically abnormal lesion cannot be visualized fully)

- HIV positive but not currently on antiviral therapy

- Performance status - 0-2

- WBC greater than 4,000/mm^3

- Absolute neutrophil count greater than 2,000/mm^3

- Platelet count normal

- Liver enzymes normal

- No liver impairment

- BUN normal

- Creatinine normal

- No renal insufficiency

- No coronary artery disease

- No cardiac arrhythmia

- No congestive heart failure

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for at least 1 month after study

- No other serious medical illness (e.g., non-insulin and insulin-dependent diabetes or connective tissue disorders)

- No other prior or concurrent malignancy

- No known G6PD deficiency

- No porphyria

- No history of 2 prior ablative/excisional therapies (i.e., cryotherapy, laser ablation, loop electrical excision procedure, or cold knife cone biopsy)

- No concurrent non-steroidal anti-inflammatory drugs (NSAIDS)

- No other concurrent significant medication/therapy such as:

- Anti-hypertensives, anti-arrhythmics, or inotropic agents for cardiopulmonary disease

- Diuretics for renal insufficiency

- Steroids or NSAIDs for connective tissue disorders

Género: Female

Edad mínima: 18 Years

Edad máxima: 65 Years

Voluntarios Saludables: No

Oficial general
Apellido Papel Afiliación
John Comerci Principal Investigator University of Pittsburgh
Ubicación
Instalaciones: University of Pittsburgh
Ubicacion Paises

United States

Fecha de verificación

February 2013

Fiesta responsable

Tipo: Sponsor

Tiene acceso ampliado No
Condición Examinar
Número de brazos 2
Grupo de brazo

Etiqueta: Part 1 (lutetium texaphyrin, LEEP)

Tipo: Experimental

Descripción: Patients receive lutetium texaphyrin IV over 5-20 minutes. Patients undergo in vivo tissue assessment by spectrometer at 0, 1, 3, 5, 12, and 24 hours and loop electrical excision procedure (LEEP) at 24 hours after lutetium texaphyrin infusion.

Etiqueta: Part 2 (lutetium texaphyrin, laser therapy, LEEP)

Tipo: Experimental

Descripción: Patients receive lutetium texaphyrin IV over 5-20 minutes. A laser delivers 730 nm of light to the cervix for 4, 8, or 16 minutes. Patients undergo LEEP at 4, 8, or 12 hours after exposure of the cervix to the light source.

Información de diseño del estudio

Asignación: Non-Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Prevention

Enmascaramiento: None (Open Label)

Fuente: ClinicalTrials.gov