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

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Terminated
CT.gov ID
NCT00005808
Collaborator
(none)
54
Enrollment
1
Location
2
Arms

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Drug: motexafin lutetium
  • Drug: photodynamic therapy
  • Procedure: loop electrosurgical excision procedure
  • Other: laboratory biomarker analysis
 Phase 1

Detailed Description

OBJECTIVES:

  1. 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).

  2. 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 Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Dec 1, 2000
Actual Primary Completion Date :
Apr 1, 2004

Arms and Interventions

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.

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

    • 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:
  • Antrin
  • lutetium texaphrin
  • lutetium texaphyrin
  • Lutex
  • PCI-0123

    • Drug: photodynamic therapy
    Undergo laser therapy
    Other Names:
  • Light Infusion Therapy™
  • PDT
  • therapy, photodynamic

    • Procedure: loop electrosurgical excision procedure
    Undergo LEEP
    Other Names:
  • LEEP
  • Loop Electrosurgical Excision

    • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1) [Up to 24 hours]

      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

    2. Maximal differential in Lutrin tissue levels between normal and dysplastic cells (Part 1) [At the time of LEEP]

    3. Percentage of tissue demonstrating PDT related effects (apoptosis/ necrosis) for normal versus abnormal epithelium at each total fluence for each LEEP cone biopsy specimen [At LEEP time]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes 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

    Locations

    Site City State Country Postal Code
    1 University of Pittsburgh Pittsburgh Pennsylvania United States 15232

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: John Comerci, University of Pittsburgh

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00005808
    Other Study ID Numbers:
    • NCI-2012-02328
    • MWH-99-077
    • U01CA099168
    • CDR0000067801
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Feb 7, 2013
    Last Verified:
    Feb 1, 2013
    Additional relevant MeSH terms:
    Neoplasms
    Carcinoma in Situ
    Cervical Intraepithelial Neoplasia
    Motexafin lutetium

    Study Results

    No Results Posted as of Feb 7, 2013