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

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

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

Study Overview

• Status: Terminated
• Conditions: Cervical Cancer; Cervical Intraepithelial Neoplasia Grade 2; Cervical Intraepithelial Neoplasia Grade 3
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: motexafin lutetium; Procedure: loop electrosurgical excision procedure; Drug: photodynamic therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Drug: motexafin lutetium; Given IV; Other Names: Antrin; lutetium texaphrin; lutetium texaphyrin; Lutex; PCI-0123; Procedure: loop electrosurgical excision procedure; Undergo LEEP; Other Names: LEEP; Loop Electrosurgical Excision
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.	Other: laboratory biomarker analysis; Correlative studies; Drug: motexafin lutetium; Given IV; Other Names: Antrin; lutetium texaphrin; lutetium texaphyrin; Lutex; PCI-0123; Procedure: loop electrosurgical excision procedure; Undergo LEEP; Other Names: LEEP; Loop Electrosurgical Excision; Drug: photodynamic therapy; Undergo laser therapy; Other Names: PDT; Light Infusion Therapy™; therapy, photodynamic

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: John Comerci, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: December 1, 2000
• Primary Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 7, 2013
• Last Update Submitted That Met QC Criteria: February 6, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Photosensitizing Agents; Dermatologic Agents; Motexafin lutetium
• Other Study ID Numbers: NCI-2012-02328; U01CA099168 (U.S. NIH Grant/Contract); MWH-99-077; CDR0000067801 (Registry Identifier: PDQ (Physician Data Query))