Photodynamic Therapy Using Lutetium Texaphyrin in Treating Patients With Cervical Intraepithelial Neoplasia
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Cervical Cancer Cervical Intraepithelial Neoplasia Grade 2 Cervical Intraepithelial Neoplasia Grade 3 |
Drug: motexafin lutetium Drug: photodynamic therapy Procedure: loop electrosurgical excision procedure Other: laboratory biomarker analysis |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | Phase I Study Photodynamic Therapy Using Lutrin (Lutetium Texaphyrin) in the Treatment of Patients With Cervical Intraepithelial Neoplasia |
- Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1) [ Time Frame: Up to 24 hours ] [ Designated as safety issue: Yes ]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
- Maximal differential in Lutrin tissue levels between normal and dysplastic cells (Part 1) [ Time Frame: At the time of LEEP ] [ Designated as safety issue: No ]
- Percentage of tissue demonstrating PDT related effects (apoptosis/ necrosis) for normal versus abnormal epithelium at each total fluence for each LEEP cone biopsy specimen [ Time Frame: At LEEP time ] [ Designated as safety issue: No ]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.
| Enrollment: | 54 |
| Study Start Date: | December 2000 |
| Primary Completion Date: | April 2004 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Part 1 (lutetium texaphyrin, LEEP)
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
Given IV
Other Names:
Procedure: loop electrosurgical excision procedure
Undergo LEEP
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
|
Experimental: Part 2 (lutetium texaphyrin, laser therapy, LEEP)
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
Given IV
Other Names:
Drug: photodynamic therapy
Undergo laser therapy
Other Names:
Procedure: loop electrosurgical excision procedure
Undergo LEEP
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
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| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00005808 History of Changes |
| Other Study ID Numbers: | NCI-2012-02328, MWH-99-077, U01CA099168, CDR0000067801 |
| Study First Received: | June 2, 2000 |
| Last Updated: | February 6, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neoplasms Uterine Cervical Neoplasms Cervical Intraepithelial Neoplasia Uterine Cervical Dysplasia Carcinoma in Situ Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Uterine Cervical Diseases Uterine Diseases Genital Diseases, Female |
Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Precancerous Conditions Motexafin lutetium Photosensitizing Agents Radiation-Sensitizing Agents Physiological Effects of Drugs Pharmacologic Actions Dermatologic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 23, 2013