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

Cervical Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00005808
• Other study ID #: NCI-2012-02328
• Secondary ID: MWH-99-077U01CA0
• Status: Terminated
• Phase: Phase 1
• First received: June 2, 2000
• Last updated: February 6, 2013
• Start date: December 2000

Study information

• Verified date: February 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 54
• Est. primary completion date: April 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Cancer
• Cervical Intraepithelial Neoplasia
• Cervical Intraepithelial Neoplasia Grade 2
• Cervical Intraepithelial Neoplasia Grade 3
• Neoplasms
• Uterine Cervical Dysplasia
• Uterine Cervical Neoplasms

Intervention

Drug:
• motexafin lutetium
Given IV
• photodynamic therapy
Undergo laser therapy

Procedure:
• loop electrosurgical excision procedure
Undergo LEEP

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	Maximal differential in Lutrin tissue levels between normal and dysplastic cells (Part 1)		At the time of LEEP	No
Primary	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	No