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

NCT ID: NCT00005808

Last Updated: 2013-02-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-12-31

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.

Conditions

Cervical Cancer; Cervical Intraepithelial Neoplasia Grade 2; Cervical Intraepithelial Neoplasia Grade 3

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

motexafin lutetium

Intervention Type: DRUG

Given IV

loop electrosurgical excision procedure

Intervention Type: PROCEDURE

Undergo LEEP

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

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.

Group Type: EXPERIMENTAL

motexafin lutetium

Intervention Type: DRUG

Given IV

photodynamic therapy

Intervention Type: DRUG

Undergo laser therapy

loop electrosurgical excision procedure

Intervention Type: PROCEDURE

Undergo LEEP

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

motexafin lutetium

Given IV

Intervention Type: DRUG

photodynamic therapy

Undergo laser therapy

Intervention Type: DRUG

loop electrosurgical excision procedure

Undergo LEEP

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Antrin; lutetium texaphrin; lutetium texaphyrin; Lutex; PCI-0123; Light Infusion Therapy™; PDT; therapy, photodynamic; LEEP; Loop Electrosurgical Excision

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Comerci

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

MWH-99-077

Identifier Type: -

Identifier Source: secondary_id

U01CA099168

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000067801

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02328

Identifier Type: -

Identifier Source: org_study_id