Phase I Study Photodynamic Therapy Using Lutrin (Lutetium Texaphyrin) in the Treatment of Patients With Cervical Intraepithelial Neoplasia
18 Years
65 Years
Female
Cervical Cancer, Cervical Intraepithelial Neoplasia Grade 2, Cervical Intraepithelial Neoplasia Grade 3
Trial Information
Phase I Study Photodynamic Therapy Using Lutrin (Lutetium Texaphyrin) in the Treatment of Patients With Cervical Intraepithelial Neoplasia
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
Outcome Measure:
Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1)
Outcome Description:
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
Outcome Time Frame:
Up to 24 hours
Safety Issue:
Yes
Principal Investigator
John Comerci
Investigator Role:
Principal Investigator
Investigator Affiliation:
University of Pittsburgh
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02328
NCT ID:
NCT00005808
Start Date:
December 2000
Completion Date:
Related Keywords:
- Cervical Cancer
- Cervical Intraepithelial Neoplasia Grade 2
- Cervical Intraepithelial Neoplasia Grade 3
- Neoplasms
- Uterine Cervical Neoplasms
- Cervical Intraepithelial Neoplasia
- Uterine Cervical Dysplasia
- Carcinoma in Situ
Name | Location |
|---|---|
| University of Pittsburgh | Pittsburgh, Pennsylvania 15261 |
