Clinical trial NCT00005808: Photodynamic Therapy Using Lutetium Texaphyrin in Treating Patients With Cervical Intraepithelial Neoplasia
Official title: Phase I Study Photodynamic Therapy Using Lutrin (Lutetium Texaphyrin) in the Treatment of Patients With Cervical Intraepithelial Neoplasia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cervical Cancer
Cervical Intraepithelial Neoplasia Grade 2
Cervical Intraepithelial Neoplasia Grade 3
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 54
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1)
timeFrame: Up to 24 hours
measure: Maximal differential in Lutrin tissue levels between normal and dysplastic cells (Part 1)
timeFrame: At the time of LEEP
measure: Percentage of tissue demonstrating PDT related effects (apoptosis/ necrosis) for normal versus abnormal epithelium at each total fluence for each LEEP cone biopsy specimen
timeFrame: At LEEP time
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: John Comerci
role: PRINCIPAL_INVESTIGATOR
References: