Clinical trial NCT00264732: A Study of Amolimogene (ZYC101a) in Patients With High Grade Cervical Intraepithelial Lesions of the Uterine Cervix
Official title: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study of Amolimogene (ZYC101a) in the Treatment of High-Grade Cervical Intraepithelial Lesions (CIN 2/3) of the Uterine Cervix
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Uterine Cervical Dysplasia
Keywords: cervical lesions
cervical dysplasia
Human papilloma virus
abnormal Pap
High-grade cervical intraepithelial lesions (CIN 2/3)
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2005-12-13
Enrollment: 251
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of amolimogene, in the treatment of patients with high-grade cervical intraepithelial lesions of the uterine cervix.

Detailed description: This is a double-blind study, so neither the patient not the doctor will know which treatment has been assigned.

Eligibility criteria: Inclusion Criteria:

To be considered for enrollment, patients must:

1. Have an abnormal Pap smear (atypical squamous cells of undetermined significance \[ASCUS\], atypical squamous cells, cannot exclude high grade \[ASC-H\], low grade squamous intraepithelial lesion \[LSIL\], high grade squamous intraepithelial lesion \[HSIL\]) result within 6 months of screening visit.
2. Have a colposcopically visible lesion suspected to be high-grade that does not involve more than 75% of the cervix.
3. Have a CIN 2/3 consensus pathology diagnosis on tissue taken from a colposcopically-directed punch biopsy.
4. Not have evidence of cervical carcinoma on Pap smear or biopsy and not have a positive endocervical curettage.
5. Not have atypical endometrial cells or glandular-cell atypia on Pap smear or biopsy.
6. Have colposcopic visualization of entire squamocolumnar junction and of the entire lesion (i.e. cannot extend into canal).
7. Not have concomitant cancer, history of malignancies, including carcinoma of the cervix, except for non-melanoma skin cancer.
8. Be willing to sign an Institutional Review Board (IRB) approved informed consent. Minors must have the consent of a parent or legal guardian as required by local laws and regulations.
9. Agree to use 2 acceptable forms of contraception (e.g., double-method including at least one barrier and one hormonal method).
10. Be capable of complying with the protocol.
11. Not have other illnesses that would put the patient at undue risk for participation in the trial or would interfere with the required clinical observations.
12. Not have abnormalities of hematological, renal, or hepatic function as determined by clinical laboratory testing.
13. Not have immunologic disorder such as immunodeficiency, lupus, or other chronic auto-immune disease.
14. Not have an active systemic infection requiring treatment.
15. Not have ongoing systemic chronic steroid therapy or immunosuppressive medication (inhalers used for treating asthma and topical steroids are permitted).
16. Not be positive for HIV antibody.
17. Not be pregnant or lactating.
18. Not plan to use a cervical cap or diaphragm during the study.
19. Not have been treated with any investigational agent within 30 days prior to randomization in this trial.
20. Not have had prior gene therapy.
21. Not have had an excisional or ablative procedure performed on the cervix within one year of enrollment.
22. Be willing to consent to an excisional procedure, such as LEEP or cold-knife cone procedure, if indicated.

Please note: There may be additional inclusion/exclusion criteria. The study center will determine if patients meet all of the criteria. If patients do not qualify for the trial, study personnel will explain the reasons. If patients do qualify, study personnel will explain the trial in detail using an IRB-approved informed consent, and answer any questions. Patients can then decide if they wish to participate.

Primary outcomes:
measure: Cervical intraepithelial neoplasia (CIN) 2/3 resolution, defined as the histological evaluation of cervical tissue (presence or absence of CIN 2/3 as determined by pathology consensus diagnosis) at the End of Observation (EOO) period.
timeFrame: 24 weeks after enrollment.
Secondary outcomes:
measure: Histology based on biopsy to determine the proportion of pts. w/resolution of CIN2/3. This is the same as primary efficacy variable in determination of presence or absence of CIN2/3, but excludes pts. with excisional procedure or cytology information.
timeFrame: 24 weeks after enrollment.
measure: Histological resolution to normal to examine the proportion of patients with a histology result of "normal" versus "abnormal."
timeFrame: 24 weeks after enrollment.
measure: Clearing or persistence of lesions based on colposcopic findings to examine the proportion of patients with "no lesion" versus "at least one lesion."
timeFrame: 24 weeks after enrollment.
measure: Pap smear cytology.
timeFrame: 24 weeks after enrollment.
measure: Clearing or persistence of original human papillomavirus (HPV) subtype as determined by HPV typing to present the number and percent of patients with absence of all HPV.
timeFrame: 24 weeks after enrollment.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Arizona Wellness Center for Women/Precision Trials, LLC
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Colton
country: United States
facility: Arrowhead Regional Medical Center
state: California
city: Palm Springs
country: United States
facility: The Center for Advanced Research and Education, Inc.
state: California
city: San Diego
country: United States
facility: Medical Center for Clinical Research
state: California
city: Lakewood
country: United States
facility: Physicians Research Options, LC
state: Colorado
city: Boynton Beach
country: United States
facility: Visions Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Florida, Miami
state: Florida
city: Sarasota
country: United States
facility: Physician Care Clinical Research
state: Florida
city: Tampa
country: United States
facility: Insignia Clinical Research
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials LLC
state: Florida
city: Augusta
country: United States
facility: Medical College of Georgia, Department of Family Medicine
state: Georgia
city: Idaho Falls
country: United States
facility: Rosemark Women's Care Specialists
state: Idaho
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: North Las Vegas
country: United States
facility: Centennial Hills OB-GYN Associaties
state: Nevada
city: Albuquerque
country: United States
facility: Southwest Clinical Research
state: New Mexico
city: Winston-Salem
country: United States
facility: Lyndhurst Gynecologic Associates
state: North Carolina
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center, Center for Research in Women's Health
state: Oklahoma
city: Philadelphia
country: United States
facility: Temple Center for Women's Health
state: Pennsylvania
city: Memphis
country: United States
facility: Sarah Cannon Research
state: Tennessee
city: Nashville
country: United States
facility: Michael Altenbern, MD
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center at Dallas
state: Texas
city: Pleasant Grove
country: United States
facility: Physicians' Research Options
state: Utah
city: Sandy
country: United States
facility: Physicians' Research Options, LLC
state: Utah
city: Virginia Beach
country: United States
facility: Tidewater Clinical Research
state: Virginia
Study officials:
References:
citation: Crum CP, Beach KJ, Hedley ML, Yuan L, Lee KR, Wright TC, Urban RG. Dynamics of human papillomavirus infection between biopsy and excision of cervical intraepithelial neoplasia: results from the ZYC101a protocol. J Infect Dis. 2004 Apr 15;189(8):1348-54. doi: 10.1086/382956. Epub 2004 Mar 30.
citation: Garcia F, Petry KU, Muderspach L, Gold MA, Braly P, Crum CP, Magill M, Silverman M, Urban RG, Hedley ML, Beach KJ. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2004 Feb;103(2):317-26. doi: 10.1097/01.AOG.0000110246.93627.17.