Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03084081 |
| Other study ID # |
17-294 |
| Secondary ID |
UH3CA189883 |
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 1, 2017 |
| Est. completion date |
July 31, 2024 |
Study information
| Verified date |
January 2024 |
| Source |
The Cleveland Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this academic-industrial partnership will compare the CryoPen® and
thermoablator to traditional CO2-based cryotherapy for the treatment of cervical precancer in
low and middle income countries (LMICs) and investigate whether the cure rates of cervical
intraepithelial neoplasia 2 and more severe diagnoses (CIN2+) with these devices are
non-inferior compared to that of conventional cryotherapy. The results of this study will
affect other research areas by serving as a springboard to exploring treatment alternatives
that are amenable to low-resource settings and thus will reach the most vulnerable
populations.
Description:
Cryotherapy is the current gold standard for treatment of precancerous cervical lesions in
low resource settings. However, in recent years a number of issues-particularly the use of
compressed gas, which requires storage and replenishment of large and potentially dangerous
tanks-have emerged as clear limitations. Two technologies-the LMICs-adapted CryoPen®,
manufactured and sold by CryoPen®, Inc. (TX, USA), and the thermoablator commercialized by
WISAP Medical Technology (Germany) are treatment options for precancerous cervical lesions
that run on electricity and avoid the difficulties associated with compressed gas. The
LMIC-adapted CryoPen® (hereafter, CryoPen®) differs from previous cryotherapy methods in that
it does not require an external source of gas (a tank), since the gas for cooling is built
into the system. Thermoablation (also called thermocoagulation) has been used since the 1970s
for treatment of cervical lesions. This is treatment with a probe heated to temperatures of
100 to 120ºC. It is also an effective, inexpensive method that does not require high-level
healthcare providers.
The purpose of this study is to conduct a randomized non-inferiority clinical trial to
compare the CryoPen® and WiSAP thermoablator to CO2-based cryotherapy for the treatment of
CIN2 or more severe diagnoses ("CIN2+") but excluding microinvasive or invasive cervical
cancer. The primary objective is to compare CIN2+ cure rates after treatment with the
LMIC-adapted CryoPen®, the WISAP thermoablator, and CO2-based cryotherapy.
Women will be recruited from the Salvadorian Social Security Hospital (ISSS) in San Salvador,
El Salvador, La Liga Contra el Cancer in Lima, Peru and Hospital Universitario San Ignacio in
Bogota, Colombia. All are referral sites for women with abnormal cytology.
The investigators will approach approximately 1,602 women with CIN2+ during a 2.5 year
enrollment phase (30 months). Assuming an approximately 80% participation rate, approximately
1,281 women will be enrolled- 1,152 (90%) will be eligible for cryotherapy (i.e. no
contraindications) and 129 will be ineligible and undergo alternative treatments. The
investigators estimate that approximately 20% will be lost to follow-up at the twelve-month
visit, so that complete data will be available on a total of 922 women (57.55% of 1,602)
treated with either CO2-based cryotherapy, LMIC-adapted CryoPen®, or thermoablation.
Eligible women with biopsy-confirmed CIN2+ will undergo HPV genotyping with next-generation
sequencing. The specimen is taken prior to treatment to establish a baseline of which HPV
types are present. If a different HPV type is present in the post-treatment specimen, this
will be classified as a new rather than persistent infection. Testing will be conducted at
the National Cancer Institute in Rockville, MD. Women will be randomly assigned to one of
three study arms:
A. CO2-based cryotherapy (double freeze), B. CryoPen® (single freeze), or C. Thermoablation
for 40 seconds at 100ºC.
At a pre-treatment visit, consented women will receive a pregnancy test as part of the
eligibility criteria for enrollment in the study. Pre-vaginal cultures will be collected to
be analyzed for bacterial vaginosis, yeast, gonorrhea and chlamydia. The same cultures will
be collected at a 6-week follow-up visit. Consented women will be enrolled and undergo a
pelvic exam and visual inspection of the cervix following placement of diluted acetic acid on
the cervix. Images of the cervix will be taken with a mobile ODT device will be taken before
and after treatment. Women deemed ineligible for cryotherapy will undergo LEEP immediately.
In the case of suspected cancer, women will be appropriately referred.
Six weeks post-treatment, women who return for a visit for evaluation of treatment side
effects; these women will complete a questionnaire to assess the presence of pain or cramps,
bleeding, stenosis, watery discharge, malodorous discharge and be evaluated for evidence of
cervicitis. In addition, vaginal cultures will be collected and analyzed for bacterial
vaginosis, yeast, gonorrhea, and chlamydia.
One year post-treatment, women will return for a follow-up visit to determine residual
disease, which is the primary endpoint. Residual disease will be determined by colposcopy and
four-quadrant biopsies. In addition, VIA, cytology, and high-risk HPV DNA testing with
careHPV will be performed. Genotyping and next-generation sequencing will be repeated to
differentiate between persistent and new infections. The goal is to evaluate sensitivity of
VIA, cytology, and HPV testing post-treatment. Women diagnosed with recurrent/untreated CIN2+
on biopsy will be asked to return to undergo LEEP. Women with suspected cancer on biopsy will
be referred to the local cancer hospital for standard of care.
