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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Cervical Cancer, Cervical Intraepithelial Neoplasia Grade 2, Cervical Intraepithelial Neoplasia Grade 3

Intervention / Treatment
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* Drug: motexafin lutetium
* Drug: photodynamic therapy
* Procedure: loop electrosurgical excision procedure
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 (lutetium texaphyrin, LEEP)<br>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. | Drug: motexafin lutetium<br>* Given IV<br>* Other names: PCI-0123;Procedure: loop electrosurgical excision procedure<br>* Undergo LEEP<br>* Other names: Loop Electrosurgical Excision;Other: laboratory biomarker analysis<br>* Correlative studies<br>|
| Experimental: Part 2 (lutetium texaphyrin, laser therapy, LEEP)<br>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. | Drug: motexafin lutetium<br>* Given IV<br>* Other names: PCI-0123;Drug: photodynamic therapy<br>* Undergo laser therapy<br>* Other names: therapy, photodynamic;Procedure: loop electrosurgical excision procedure<br>* Undergo LEEP<br>* Other names: Loop Electrosurgical Excision;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1) | A simplified graphical analysis will be utilized to determine the drug dose and time after administration that provides the largest differential area between lutein texaphyrin tissue levels in neoplastic and normal cervical tissue | 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 | A simplified graphical analysis will be utilized to determine the fluence that provides the maximal differential area between neoplastic and normal cervical epithelium and stroma. | At LEEP time |