- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03429582
Comparison of Cervical CIN II/III Treatment Outcomes With Thermal Ablation Device
Comparison of Cervical Intraepithelial Neoplasia 2/3 Treatment Outcomes With a Portable LMIC-adapted Thermal Ablation Device vs. Gas-based Cryotherapy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The standard treatment for cervical pre-cancer is gas-based cryotherapy, the freezing of tissue to ablate (destroy) lesions. Although cryotherapy is relatively simple to perform, the necessary gas tanks are generally expensive, difficult to obtain and transport, and pose a danger of explosion. An urgent need exists for a point-of-care treatment technology that is accessible, portable, and inexpensive. An alternative ablative procedure in use since the 1970s is thermoablation (also known as cold coagulation or thermocoagulation), which utilizes heat to destroy pre-cancer. Despite its long-standing use, there are no standardized guidelines for thermoablation. There is also little data on patient and provider acceptability, potential side effects, and the impact of different treatment protocols on quality of life. For these reasons, international and national agencies have been hesitant to adopt the technique as an alternative to cryotherapy. The purpose of this research study is to develop a patient-centered thermoablation protocol that is simple, safe, and effective.
Currently, the most common treatment technique for thermoablation involves a multiple-tip protocol, which uses differently shaped probe-tips to cover the affected area. This technique requires a considerable degree of expertise, and may not be the most appropriate strategy for settings where highly trained healthcare providers are scarce. In collaboration with WiSAP Medical Technology (Brunnthal, Germany), the manufacturer of the most widely used thermoablator, the investigators modified the original device to meet the needs of low-resource settings. The LMIC-adapted thermoablator is lightweight, portable, and easy to operate. The investigators will further modify the LMIC-adapted thermoablator to test the non-inferiority of two thermoablation treatment approaches against the standard of care (i.e. gas-based cryotherapy). The experimental approaches include:
- Single tip: A 19mm conical tip with a nipple is applied to the cervix for 40-seconds at 100ºC, a single application of which should ablate the squamocolumnar junction (SCJ) in the majority of women. In the rare instance that the SCJ is not completely ablated, additional 20 second applications can be applied, or
- Multiple tips: A narrow nipple shaped tip at 100ºC is placed in the endocervix for 20 seconds. This is followed by the placement of a 12 mm flat tip at 100ºC on the ectocervix for as many 20-second applications as necessary to ablate the entire SCJ.
These will be tested against traditional CO2 cryotherapy treatment using a MedGyn device in a standard double-freeze procedure (3 minute freeze, 5 minute thaw, 3 minute freeze).
Women will be recruited at colposcopy clinics run by the Ministry of Health and the Mexican Institute of Social Security (Instituto Mexicano del Seguro Social) in the Mexico City metropolitan region. Eligible women will be those over the age of 18, who are able and willing to provide informed consent and a reliable or permanent address, and with a biopsy-confirmed CIN2+ diagnosis. Women wo are pregnant, plan to become pregnant during the study duration, with a history of total hysterectomy, past surgeries destructive to the cervix within the last 5 years, with a disfigure or hard-to-reach cervix, and those with contraindications for ablative treatment will be excluded from the study.
The investigators will approach 1,602 women with CIN2+ during a four-year enrollment phase (48 months). Assuming an 80% participation rate, approximately 1,282 women will be enrolled; of these, 1,155 (90%) will be eligible for ablation treatment (i.e. no contraindications) and 129 will be ineligible and undergo alternative treatments (i.e. LEEP or invasive cancer treatment). The investigators estimate that approximately 20% will be lost to follow-up at the 12-month visit, resulting in complete data on a total of 924 women (57.7% of 1,602) treated with CO2-based cryotherapy, single-tip thermoablation, or multiple-tip thermoablation. The investigators will monitor the percentages of ineligible women, contraindications, and loss to follow-up in real time and adjust recruitment accordingly to achieve the target sample size.
The clinical endpoint of the study will be residual disease at the 12-month follow-up visit as determined by colposcopy, four-quadrant biopsy, and endocervical curettage (ECC). HPV testing will also be performed at this visit to differentiate between persistent or new infection. Cytology, VIA and care HPV tests will also be performed to evaluate the most effective post treatment screening strategy.
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 colposcopy device will be taken before and after treatment. Women will be asked to evaluate their pain level after speculum insertion, immediately before treatment, and immediately after treatment. These women will also complete a quality of life assessment. 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 be administered a post-treatment patient satisfaction survey, and 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 investigators will evaluate sensitivity of VIA, cytology, and HPV testing post-treatment. Women will be asked to again complete the quality of life assessment and treatment acceptability instrument. 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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Miriam Cremer, MD
- Phone Number: 216-312-0618
- Email: cremerm@ccf.org
Study Contact Backup
- Name: Montserrat Soler, PhD
- Phone Number: 619-980-0157
- Email: solerm@ccf.org
Study Locations
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Shenzhen, China
- Peking University Shenzhen Hospital
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San Salvador, El Salvador
- Hospital Nacional de la Mujer
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Criteria for inclusion
- Women aged 18 and older
- Biopsy results of CIN2, CIN2-3, CIN3, or high-grade CIN not otherwise specified
- Willing and able to provide informed consent
- Willing and able to provide permanent or reliable address
Criteria for exclusion
- Pregnant or plans to become pregnant during study
- History of total hysterectomy (verified by medical record or pelvic evaluation)
- Previous surgery destructive to the cervix within the last 5 years
- Patient not eligible for cryotherapy or thermoablation (lesion >75% of cervix, lesion extends into canal or there is suspicion for invasive cancer)
- Cervix shape disfigured or hard to reach
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Standard C02 Cryotherapy
Standard therapy using carbon dioxide for freezing of tissue
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Standard therapy using carbon dioxide for freezing of tissue
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Experimental: Single Tip Thermoablation
Thermoablator outfitted with a 19mm conical tip
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Thermoablator outfitted with a 19mm conical tip
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Experimental: Multiple Tip Thermoablation
Thermoablator outfitted with detachable probes
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Thermoablator outfitted with detachable probes
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Residual CIN2+ diagnosis of recurrent and or untreated cervical intraepithelial neoplasia grade 2 or with cervical cancer diagnosis Diagnosis of recurrent and or untreated cervical intraepithelial neoplasia grade 2 or with cervical cancer diagnosis
Time Frame: 12-months post treatment
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To compare CIN2+ cure rates 12-months post-treatment for CO2-based cryotherapy and both single versus multiple tips thermoablation strategies
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12-months post treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient's pain assessed using the Wong-Baker FACES scale
Time Frame: Immediately after speculum insertion, immediately before treatment, and immediately after treatment
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Functional Assessment of Chronic Illness Therapy for Patients with Cervical Dysplasia Version 4 (FACIT-CD). Consists of 5-subscales listed below. For all subscales and the scale, 0 is the worst outcome, higher scores are better outcomes. All subscales are summed. Subscale ranges are as follows: Physical well-being:0 to 32, Treatment satisfaction:0 to 16, General perceptions:0 to 28, Emotional well-being:0 to 44, Relationship support: 0 to 16 Wong-Baker FACES® Pain Rating Scale, construct being measured is pain for anyone over the age of 3. Scale range: Minimum = 0, Maximum = 10. For each scale range, what is a better or worse outcome: 0 is a better outcome (no pain), higher scores are worse outcomes, and 10 is the worst outcome (worst pain). There are no subscales. |
Immediately after speculum insertion, immediately before treatment, and immediately after treatment
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient's satisfaction with treatment assessed with the FACIT-CD questionnaire (FACIT Measurement System)
Time Frame: At enrollment, 6-week visit, and 12-month follow-up visit
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FACIT-CD Version 4: 5-subscales.
For all subscales and the scale, 0 is the worst outcome, higher scores are better outcomes.
All subscales are summed.
Subscale ranges are as follows: Physical well-being:0 to 32, Treatment satisfaction: 0 to 16, General perceptions: 0 to 28, Emotional well-being:0 to 44, Relationship support: 0 to 16
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At enrollment, 6-week visit, and 12-month follow-up visit
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Patient's hope for the future using the Herth Hope Index
Time Frame: At enrollment and at 12-month follow-up visit
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Herth Hope Index.
The construct is hope in adults in clinical settings.
Scale ranges: 1 to 4. For the total index, 12 is the worst outcome.
Higher scores are better outcomes.
There are no subscales.
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At enrollment and at 12-month follow-up visit
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Miriam Cremer, MD, The Cleveland Clinic
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Uterine Cervical Diseases
- Uterine Diseases
- Precancerous Conditions
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Neoplasms
- Carcinoma in Situ
- Uterine Cervical Dysplasia
Other Study ID Numbers
- 17-1385
- 1R01CA218195-01A1 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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