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

Brief Title

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

Official Title

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

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.
    

Study Phase

Phase 1

Study Type

Interventional

Primary Outcome

Optimal dosage with the least toxicity of lutetium texaphyrin (Part 1)

Condition

Cervical Cancer

Intervention

motexafin lutetium

Study Arms / Comparison Groups

 Part 1 (lutetium texaphyrin, LEEP)

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

54

Start Date

December 2000

Primary Completion Date

April 2004

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
      

Gender

Female

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

John Comerci, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00005808

Organization ID

NCI-2012-02328

Secondary IDs

MWH-99-077

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)

Study Sponsor

John Comerci, Principal Investigator, University of Pittsburgh

Verification Date

February 2013