Screen and Treat for Cervical Cancer Prevention

Cervical Cancer Clinical Trial

— SAT  

Official title:

Safety and Efficacy of Two Screen-and-Treat Approaches for the Prevention of Cervical Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00233727
• Other study ID #: AAAB3373
• Status: Terminated
• Phase: Phase 3
• First received: October 4, 2005
• Last updated: July 7, 2015
• Start date: January 2000
• Est. completion date: May 2013

Study information

• Verified date: July 2015
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The study measures the impact of "screen-and-treat" on the prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+). It is a three-arm, randomized clinical trial comparing two "screen-and-treat" approaches to delayed evaluation as a control. The primary outcome is biopsy-confirmed CIN 2+ at 6 months and significant complications within 6 months of randomization with continued follow-up to detect CIN2+ and other complications up to 36 months post-randomization.

Description:

Participants and Clinical Examinations: Unscreened, non-pregnant women 35-65 years of age are enrolled at three closely located clinical sites in Khayelitsha, South Africa. All women provide informed consent, receive counseling for confidential HIV serotesting, a questionnaire, a pregnancy test if not postmenopausal, anonymous HIV serotesting, and a vaginal speculum examination by nurses trained in visual inspection of the cervix with acetic acid (VIA). Cervical specimens are obtained for testing for N. gonorrhea, Chlamydia trachomatis and high-risk types of HPV, and cytology. The cervix is washed with 5% acetic acid and inspected for gross abnormalities or areas of acetowhitening and a 35 mm. photograph taken. Women with significant cervicitis or vulvovaginitis are treated using the syndromic approach. N. gonorrhea or Chlamydia trachomatis positive women receive appropriate therapy. A positive VIA examination is defined as any acetowhite lesion and no attempt is made to differentiate the acetowhitening of metaplasia from CIN. Women with lesions suspicious for cancer, large acetowhite lesions extending over 70% of the cervix or into endocervical canal, and 374 unsuitable for cryotherapy due to severe atrophy, polyps, cervix distorted, cervix not adequately visualized are excluded. These women are referred to colposcopy.

Women are asked to return 2-6 days later for randomization to either: (1) HPV arm in which all HPV DNA positive women receive cryotherapy; (2) VIA arm in which all VIA positive women receive cryotherapy; and (3) a delayed evaluation arm in which women are followed untreated, irrespective of HPV or VIA status. Randomization is done at a patient level using a computer-generated randomization schedule with arm assignments provided to the clinics in sealed envelopes. Cryotherapy is performed by a nurse using N2O and a cryosurgical unit (Wallach Surgical Devices, Orange, CT) using two 3-minute freezes. Cytology results are not available at the time of cryotherapy. Both treated and untreated women are asked to return at 4 weeks for a questionnaire.

At 6 months, colposcopy is done by a physician blinded to arm and clinical information. All acetowhite lesions are biopsied and all have an endocervical curettage. Women with CIN 2+ are treated with LEEP. Examinations in women who became pregnant during the study are postponed until three months post-partum. Blood for anonymous HIV serotesting is obtained. All women who were HPV or VIA-positive at enrollment and a subset who were HPV and VIA-negative (all women enrolled in 2002) are scheduled for repeat colposcopy at 12 months, 24 months and 36 months post-randomization. At these visits, cervical samples are collected and colposcopy and biopsy if indicated is performed.

Laboratory Testing: HPV testing is done using the Hybrid Capture 2 HPV DNA assay and high-risk probe mixture (Digene Corporation, Gaithersburg, MD) at the University of Cape Town. Biopsies are processed at Columbia University and blindly evaluated by a single pathologist.

Other known NCT identifiers

• NCT00494000

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7123
• Est. completion date: May 2013
• Est. primary completion date: April 2006
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 35 Years to 65 Years

Eligibility

Inclusion Criteria:

• Has a cervix

• Never been screened for cervical cancer

• Not currently pregnant

Exclusion Criteria:

• Has previously had a Pap smear

• Has previously undergone treatment for cervical squamous intraepithelial lesion (SIL)

• Have lesions suspicious for cancer, have large acetowhite lesions extending over 70% of the cervix or into endocervical canal, are unsuitable for cryotherapy because of severe atrophy, polyps, cervix distorted, cervix cannot be adequately visualized

• Is unable to cooperate with study procedures or tolerate the insertion of a speculum

Study Design

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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Procedure:
• HPV DNA Testing + Cryosurgery
Patients will undergo a "Screen and Treat" program utilizing HPV DNA testing of clinician-collected cervical samples, followed by cryosurgery of screen positive women.
• VIA + Cryosurgery
Patients will undergo a "Screen and Treat" program utilizing visual inspection of the cervix with acetic acid (VIA), followed by cryosurgery of screen positive women.

Locations

Country	Name	City	State
South Africa	University of Cape Town	Cape Town	Western Cape

Sponsors (4)

Lead Sponsor	Collaborator
Columbia University	Bill and Melinda Gates Foundation, EngenderHealth, University of Cape Town

Country where clinical trial is conducted

South Africa, 

References & Publications (1)

Denny L, Kuhn L, De Souza M, Pollack AE, Dupree W, Wright TC Jr. Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial. JAMA. 2005 Nov 2;294(17):2173-81. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of "Screen and Treat" + Cryosurgery	Cervical Intraepithelial Neoplasia (CIN) Grade 2 or 3 or Cervical Cancer: To determine the reduction in prevalence of biopsy-confirmed high-grade SIL (HiSIL) when a "Screen and Treat" program utilizing visual inspection of the cervix with acetic acid (VIA) or HPV DNA followed by immediate cryosurgery of screen positive women is carried out by mid-level practitioners without the use of colposcopy in a low-resource setting.	Up to 12 months from entry into the study	No
Secondary	HIV incidence	Comparison of the rates of HIV seroconversion in women treated using cryosurgery with that of demographically similar, untreated women.	6 months after entry into study	No
Secondary	Safety of Cryosurgery	To determine the complication rate of cryosurgery by evaluating the occurrence of any severe adverse events (e.g. bleeding, infection)associated with the use of cryosurgery.	Up to 12 months from entry into study	Yes