The Use of the LuViva Advanced Cervical Scan to Identify Women at High-Risk for Cervical Neoplasia

Cervical Dysplasia Clinical Trial

Official title:

The Use of the LuViva Advanced Cervical Scan to Identify Women at High-Risk for Cervical Neoplasia

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04915495
• Other study ID #: CC-03-01-2020
• Status: Enrolling by invitation
• Phase: N/A
• Start date: May 5, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Guided Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to demonstrate that a multimodal hyperspectral device (LuViva) is able to segregate women with abnormal screening tests into Low and High risk groups for the purpose of determining whether they require enhanced colposcopy and additional biopsies in order to increase detection of CIN2+ cervical disease.

Description:

This study is a matched pair design, single-arm study with the following two treatments: current standard of care (SOC) and the LuViva study device. After undergoing the LuViva test, all study subjects will first undergo the SOC (i.e., nominal) colposcopy, with the colposcopist noting on the case report form (CRF), locations of lesions with colposcopy impression of CIN1+. Then the colposcopist will employ enhanced colposcopy measures that include the use on Lugol's solution and green/blue filters. The colposcopist will note on the CRF any additional lesions that became evident as a result of these enhanced measures, regardless of colposcopic impression. Biopsies of these lesions will be taken. Biopsies identified using SOC practices will be placed in vials labeled "SOC Samples". Biopsies identified using enhanced practices will be placed in vials labeled "Additional Samples". The colposcopist will then take a biopsy from any quadrant at the squamocolumnar junction (SCJ) in which a lesion was not observed. These biopsies will be placed in the vial labeled "Additional Samples". Once all colposcopy procedures are completed, biopsies of lesions collected, and biopsies of any non-lesion identified quadrants collected, an ECC, if indicated, will be collected. If an ECC would have been taken per SOC practices, it will be placed in a vial labeled "SOC ECC". ECCs collected per enhanced procedures will be placed in a vial labeled "Additional ECC". The study is a matched pair design because all subjects are tested with the LuViva device, and all will undergo both the nominal (minimal) colposcopy and biopsy treatment pursuant to ASCCP Guidelines as well as enhanced colposcopy and biopsy. By analyzing all biopsy specimens from SOC procedures and enhanced procedures, it can be determined 1) Whether enhanced procedures can be justified when the LuViva test indicates High-risk by the increase in detection of CIN2+ and 2) That when LuViva indicates Low-risk, that enhanced procedures (in the absence of a LuViva High-risk result) are not the reason for increased detection of CIN2+. Subjects will be enrolled during their normally scheduled colposcopy visit and will be recruited from the pool of patients that are referred to colposcopy based on the ASCCP Guidelines published in April 2020. The total number of enrolled female subjects pooled across all clinical sites combined will not exceed 500 in order to target an evaluable cohort of approximately 400 women.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 400
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Able to read or understand and give informed consent

• Referral Pap test within 120 days

• Scheduled for colposcopy based on the 2019 ASCCP Management Guidelines that fall within the 4% to 59% Immediate CIN3+ risk with the exception of women who lack a cervix or may be pregnant and are recommended to colposcopy.*

• Notes: The rationale for defining the referral inclusion criteria as women scheduled for colposcopy is that this group has been identified with having a significant likelihood of being diagnosed with CIN2+ over the two year period after being referred to colposcopy because of an abnormal screening test or tests. For example, the ALTS results showed that women with ASC-US plus high-risk HPV, LSIL, ASC-H, AGC and HSIL all had a likelihood of CIN2+ of approximately 10% to 20% or greater in the cases of ASC-H and HSIL (5). More recently, it has been shown that this threshold also carries with it a 4% or greater likelihood of immediate CIN3+ (12).

Exclusion Criteria:

• Pregnancy

• Menstruating on the day of colposcopy and LuViva test

• Radiation therapy to her genitourinary system within 1 year

• Prior hysterectomy in which cervix was removed

• Congenital anatomical cervical variant (e.g., double cervix)

• Friable cervix at the time of the study (i.e., a cervix that bleeds easily upon minimal contact or trauma)

• Post-coital or other significant bleeding at the time of the exam

• Excessive cervical mucous or discharge that cannot be removed and is significant enough, in the opinion of the Investigator, to interfere with a Pap test or colposcopy, resulting from inflammation, bacterial infection or other sources

• History of any photosensitizing disease or other disease affected by Ultra-violet radiation, (e.g., pophyria, Lupus Erythematosus).

• Undergoing phototherapy

• Recent use of photosensitizing agents, such as fluoroquinolones or retinoids

• Under-screened populations - defined as those women who have not been screened within the past 5 years who also screen positive for any HPV genotype

Related Conditions & MeSH terms

• Cervical Dysplasia
• Uterine Cervical Dysplasia

Intervention

Diagnostic Test:
• LuViva Advanced Cervical Scan
Multimodal hyperspectral device

Locations

Country	Name	City	State
United States	Emory University- Winship Cancer Institute	Atlanta	Georgia
United States	Great Lakes Bay Health Centers	Bay City	Michigan
United States	University of Alabama Birmingham- Heersink School of Medicine	Birmingham	Alabama
United States	Tidewater Clinical Research	Norfolk	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Guided Therapeutics

Country where clinical trial is conducted

United States, 

References & Publications (23)

ASCUS-LSIL Traige Study (ALTS) Group. Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 2003 Jun;188(6):1383-92. doi: 10.1067/mob.2003.457. — View Citation

Baasland I, Hagen B, Vogt C, Valla M, Romundstad PR. Colposcopy and additive diagnostic value of biopsies from colposcopy-negative areas to detect cervical dysplasia. Acta Obstet Gynecol Scand. 2016 Nov;95(11):1258-1263. doi: 10.1111/aogs.13009. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Cheung LC, Egemen D, Chen X, Katki HA, Demarco M, Wiser AL, Perkins RB, Guido RS, Wentzensen N, Schiffman M. 2019 ASCCP Risk-Based Management Consensus Guidelines: Methods for Risk Estimation, Recommended Management, and Validation. J Low Genit Tract Dis. 2020 Apr;24(2):90-101. doi: 10.1097/LGT.0000000000000528. — View Citation

Gage JC, Hanson VW, Abbey K, Dippery S, Gardner S, Kubota J, Schiffman M, Solomon D, Jeronimo J; ASCUS LSIL Triage Study (ALTS) Group. Number of cervical biopsies and sensitivity of colposcopy. Obstet Gynecol. 2006 Aug;108(2):264-72. doi: 10.1097/01.AOG.0000220505.18525.85. — View Citation

Hu SY, Zhang WH, Li SM, Li N, Huang MN, Pan QJ, Zhang X, Han Y, Zhao FH, Chen W, Qiao YL. Pooled analysis on the necessity of random 4-quadrant cervical biopsies and endocervical curettage in women with positive screening but negative colposcopy. Medicine (Baltimore). 2017 Apr;96(17):e6689. doi: 10.1097/MD.0000000000006689. — View Citation

Huh WK, Papagiannakis E, Gold MA. Observed Colposcopy Practice in US Community-Based Clinics: The Retrospective Control Arm of the IMPROVE-COLPO Study. J Low Genit Tract Dis. 2019 Apr;23(2):110-115. doi: 10.1097/LGT.0000000000000454. — View Citation

Jeronimo J, Schiffman M. Colposcopy at a crossroads. Am J Obstet Gynecol. 2006 Aug;195(2):349-53. doi: 10.1016/j.ajog.2006.01.091. Epub 2006 May 3. — View Citation

Massad LS, Collins YC. Strength of correlations between colposcopic impression and biopsy histology. Gynecol Oncol. 2003 Jun;89(3):424-8. doi: 10.1016/s0090-8258(03)00082-9. — View Citation

Mitchell MF, Schottenfeld D, Tortolero-Luna G, Cantor SB, Richards-Kortum R. Colposcopy for the diagnosis of squamous intraepithelial lesions: a meta-analysis. Obstet Gynecol. 1998 Apr;91(4):626-31. doi: 10.1016/s0029-7844(98)00006-4. — View Citation

Nam K, Chung S, Kwak J, Cha S, Kim J, Jeon S, Bae D. Random biopsy after colposcopy-directed biopsy improves the diagnosis of cervical intraepithelial neoplasia grade 2 or worse. J Low Genit Tract Dis. 2010 Oct;14(4):346-51. doi: 10.1097/LGT.0b013e3181e9635b. — View Citation

Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, Huh WK, Kim JJ, Moscicki AB, Nayar R, Saraiya M, Sawaya GF, Wentzensen N, Schiffman M; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020 Apr;24(2):102-131. doi: 10.1097/LGT.0000000000000525. No abstract available. Erratum In: J Low Genit Tract Dis. 2020 Oct;24(4):427. — View Citation

Pretorius RG, Belinson JL, Azizi F, Peterson PC, Belinson S. Utility of random cervical biopsy and endocervical curettage in a low-risk population. J Low Genit Tract Dis. 2012 Oct;16(4):333-8. doi: 10.1097/LGT.0b013e3182480c18. — View Citation

Pretorius RG, Belinson JL. Colposcopy. Minerva Ginecol. 2012 Apr;64(2):173-80. — View Citation

Sawaya GF, Kuppermann M. Identifying a "range of reasonable options" for cervical cancer screening. Obstet Gynecol. 2015 Feb;125(2):308-310. doi: 10.1097/AOG.0000000000000670. No abstract available. — View Citation

Sherman ME, Schiffman M, Cox JT; Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study Group. Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst. 2002 Jan 16;94(2):102-7. doi: 10.1093/jnci/94.2.102. — View Citation

Stoler MH, Vichnin MD, Ferenczy A, Ferris DG, Perez G, Paavonen J, Joura EA, Djursing H, Sigurdsson K, Jefferson L, Alvarez F, Sings HL, Lu S, James MK, Saah A, Haupt RM; FUTURE I, II and III Investigators. The accuracy of colposcopic biopsy: analyses from the placebo arm of the Gardasil clinical trials. Int J Cancer. 2011 Mar 15;128(6):1354-62. doi: 10.1002/ijc.25470. — View Citation

Twiggs LB, Chakhtoura NA, Ferris DG, Flowers LC, Winter ML, Sternfeld DR, Lashgari M, Burnett AF, Raab SS, Wilkinson EJ. Multimodal hyperspectroscopy as a triage test for cervical neoplasia: pivotal clinical trial results. Gynecol Oncol. 2013 Jul;130(1):147-51. doi: 10.1016/j.ygyno.2013.04.012. Epub 2013 Apr 13. — View Citation

van der Marel J, van Baars R, Rodriguez A, Quint WG, van de Sandt MM, Berkhof J, Schiffman M, Torne A, Ordi J, Jenkins D, Verheijen RH, Helmerhorst TJ, Ter Harmsel B, Wentzensen N, Del Pino M. The increased detection of cervical intraepithelial neoplasia when using a second biopsy at colposcopy. Gynecol Oncol. 2014 Nov;135(2):201-7. doi: 10.1016/j.ygyno.2014.08.040. Epub 2014 Sep 7. — View Citation

Waxman AG, Conageski C, Silver MI, Tedeschi C, Stier EA, Apgar B, Huh WK, Wentzensen N, Massad LS, Khan MJ, Mayeaux EJ Jr, Einstein MH, Schiffman MH, Guido RS. ASCCP Colposcopy Standards: How Do We Perform Colposcopy? Implications for Establishing Standards. J Low Genit Tract Dis. 2017 Oct;21(4):235-241. doi: 10.1097/LGT.0000000000000336. — View Citation

Wentzensen N, Massad LS, Mayeaux EJ Jr, Khan MJ, Waxman AG, Einstein MH, Conageski C, Schiffman MH, Gold MA, Apgar BS, Chelmow D, Choma KK, Darragh TM, Gage JC, Garcia FAR, Guido RS, Jeronimo JA, Liu A, Mathews CA, Mitchell MM, Moscicki AB, Novetsky AP, Papasozomenos T, Perkins RB, Silver MI, Smith KM, Stier EA, Tedeschi CA, Werner CL, Huh WK. Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States. J Low Genit Tract Dis. 2017 Oct;21(4):216-222. doi: 10.1097/LGT.0000000000000322. — View Citation

Wentzensen N, Walker JL, Gold MA, Smith KM, Zuna RE, Mathews C, Dunn ST, Zhang R, Moxley K, Bishop E, Tenney M, Nugent E, Graubard BI, Wacholder S, Schiffman M. Multiple biopsies and detection of cervical cancer precursors at colposcopy. J Clin Oncol. 2015 Jan 1;33(1):83-9. doi: 10.1200/JCO.2014.55.9948. Epub 2014 Nov 24. — View Citation

Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ; ASCCP-Sponsored Consensus Conference. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002 Apr 24;287(16):2120-9. doi: 10.1001/jama.287.16.2120. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of Diagnostic Device	LuViva's ability to correctly identify diseased tissue. LuViva result indicated High-risk and the pathology results indicate the presence of disease cervical tissue.	up to 60 days after completion of enrollment
Secondary	Specificity of Diagnostic Device	LuViva's ability to correctly identify non diseased tissue. LuViva result indicated Low-risk and the pathology results did not indicate the presence of disease cervical tissue.	up to 60 days after completion of enrollment