Evaluation of the Cobas® 4800 HPV Test for the Detection of High-grade Cervical Disease

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00709891
• Collaborator: (none)
• Enrollment: 47,208
• Locations: 61
• Arm: 1
• Duration (Months): 61
• Patients Per Site: 773.9
• Patients Per Site Per Month: 12.7

Study Details

Study Description

Brief Summary

This study provided data on the performance of the Cobas® 4800 HPV Test for identifying histologically confirmed high-grade cervical disease. The baseline, cross-sectional phase was conducted in approximately 45,000 women undergoing routine cervical cancer screening, of whom approximately 7,400 were selected to undergo colposcopy and biopsy/endocervical curettage (ECC) at baseline. These subjects included women with cytology that is 'not normal' and a selection of those with 'normal' cytology who entered a follow-up phase and underwent cytological evaluation annually for 3 years. In this follow-up phase, colposcopy and biopsy/ECC were performed only in women with cervical cytology considered 'not normal' at any of the annual follow-up visits.

Condition or Disease	Intervention/Treatment	Phase
Human Papilloma Virus (HPV)	Device: cobas® 4800 HPV Test	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 47208 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of the Cobas® 4800 HPV Test for the Detection of High-grade Cervical Disease in Women Undergoing Routine Cervical Cancer Screening
• Study Start Date: May 1, 2008
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cobas® 4800 HPV Test The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.	Device: cobas® 4800 HPV Test

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Diagnosis of ≥ CIN2 [Baseline to the end of the Baseline period (up to 12 weeks)]

   A diagnosis of ≥ CIN2 (cervical intraepithelial neoplasia) included histology results of CIN2, CIN3, adenocarcinoma in situ, squamous cell carcinoma, or adenocarcinoma. The diagnosis was based on central pathology review.

Secondary Outcome Measures

1. Percentage of Participants With a Diagnosis of ≥ CIN3 [Baseline to the end of the study (up to 5 years, 1 month)]

   A diagnosis of ≥ CIN3 (cervical intraepithelial neoplasia) included histology results of CIN3, adenocarcinoma in situ, squamous cell carcinoma, or adenocarcinoma. The diagnosis was based on central pathology review.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Females ≥ 21 years of age presenting for routine cervical cancer screening.

• An intact cervix.

• Willing and able to undergo colposcopy and biopsy and endocervical curettage within 8 weeks after study Visit 1.

Exclusion Criteria:

• Known pregnancy at study Visit 1.

• Presenting for colposcopy at study Visit 1.

• Any condition resulting in increased risk of bleeding at biopsy.

• Hysterectomy.

• Known history of ablative or excisional therapy to the cervix within the preceding 12 months.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Enterprise	Alabama	United States	36331
2		Hoover	Alabama	United States	35216
3		Mobile	Alabama	United States	36608
4		Phoenix	Arizona	United States	85015
5		Phoenix	Arizona	United States	85032
6		Tucson	Arizona	United States	85712
7		Tucson	Arizona	United States	85755
8		Beverly Hills	California	United States	90211
9		Carmichael	California	United States	95608
10		Costa Mesa	California	United States	92617
11		Fountain Valley	California	United States	92708-5153
12		San Diego	California	United States	92123
13		Colorado Springs	Colorado	United States	80910
14		Lakewood	Colorado	United States	80228
15		Boynton Beach	Florida	United States	8188
16		Ft. Lauderdale	Florida	United States	33316
17		Jacksonville	Florida	United States	32216
18		Jacksonville	Florida	United States	32259
19		Jupiter	Florida	United States	33458
20		Lake Worth	Florida	United States	33461
21		Miami	Florida	United States	33143
22		North Miami	Florida	United States	33161
23		Sarasota	Florida	United States	34239
24		Tampa	Florida	United States	33613
25		West Palm Beach	Florida	United States	33401
26		West Palm Beach	Florida	United States	33409
27		Atlanta	Georgia	United States	30328
28		Decatur	Georgia	United States	30033
29		Roswell	Georgia	United States	30075
30		Boise	Idaho	United States	83712
31		Champaign	Illinois	United States	61820
32		Indianapolis	Indiana	United States	46268
33		Newburgh	Indiana	United States	47360
34		Louisville	Kentucky	United States	40291
35		Paducah	Kentucky	United States	42003
36		Covington	Louisiana	United States	70433
37		Ruston	Louisiana	United States	71270
38		Saginaw	Michigan	United States	48604
39		Las Vegas	Nevada	United States	89106
40		Lawrenceville	New Jersey	United States	08648
41		Moorestown	New Jersey	United States	08057
42		Albuquerque	New Mexico	United States	87102
43		New Bern	North Carolina	United States	28562
44		Winston-Salem	North Carolina	United States	27103
45		Englewood	Ohio	United States	45342
46		Lansdale	Pennsylvania	United States	19446
47		West Reading	Pennsylvania	United States	19611
48		Columbia	South Carolina	United States	29201
49		Hilton Head	South Carolina	United States	29926
50		North Charleston	South Carolina	United States	29406
51		Chattanooga	Tennessee	United States	37404
52		Johnson City	Tennessee	United States	37604
53		Nashville	Tennessee	United States	37203
54		Corpus Christi	Texas	United States	78414
55		Dallas	Texas	United States	75230
56		Houston	Texas	United States	77054
57		McAllen	Texas	United States	78503
58		Temple	Texas	United States	76508
59		Salt Lake City	Utah	United States	84107
60		Virginia Beach	Virginia	United States	23456
61		Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Catherine Behrens, Roche Molecular Systems, Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00709891
• Other Study ID Numbers: RD000649; MWP-HPV-159
• First Posted: Jul 3, 2008
• Last Update Posted: Feb 9, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Papilloma; Uterine Cervical Diseases

Study Results

Participant Flow

Pre-assignment Detail	Participants who had not met the study primary clinical endpoint of ≥ CIN2 were invited to participate in the longitudinal follow-up phase.

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Period Title: Baseline, Cross-sectional Phase
STARTED	47208
COMPLETED	45758
NOT COMPLETED	1450
Period Title: Baseline, Cross-sectional Phase
STARTED	10002
COMPLETED	5020
NOT COMPLETED	4982

Baseline Characteristics

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Overall Participants	46887
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.8 (12.3)
Sex: Female, Male (Count of Participants)
Female	46887 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Diagnosis of ≥ CIN2
Description	A diagnosis of ≥ CIN2 (cervical intraepithelial neoplasia) included histology results of CIN2, CIN3, adenocarcinoma in situ, squamous cell carcinoma, or adenocarcinoma. The diagnosis was based on central pathology review.
Time Frame	Baseline to the end of the Baseline period (up to 12 weeks)

Outcome Measure Data

Analysis Population Description

Evaluable ASC-US participant population: All enrolled participants with a diagnosis of atypical squamous cells of undetermined significance (ASC-US).

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Measure Participants	1578
Positive cobas 4800 HPV test result - n=514	14.0 0%
Negative cobas 4800 HPV test result - n=1064	0.8 0%

2. Secondary Outcome

Title	Percentage of Participants With a Diagnosis of ≥ CIN3
Description	A diagnosis of ≥ CIN3 (cervical intraepithelial neoplasia) included histology results of CIN3, adenocarcinoma in situ, squamous cell carcinoma, or adenocarcinoma. The diagnosis was based on central pathology review.
Time Frame	Baseline to the end of the study (up to 5 years, 1 month)

Outcome Measure Data

Analysis Population Description

Evaluable ASC-US participant population: All enrolled participants with a diagnosis of atypical squamous cells of undetermined significance (ASC-US).

Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
Measure Participants	1578
Positive cobas 4800 HPV test result - n=514	8.4 0%
Negative cobas 4800 HPV test result - n=1064	0.3 0%

Adverse Events

Adverse Event Reporting Description	Safety population: All enrolled participants. Non-serious adverse events were not recorded in this study.
Arm/Group Title	Cobas® 4800 HPV Test
Arm/Group Description	The cobas 4800 human papillomavirus (HPV) Test combines in a single assay the identification of pooled high-risk oncogenic HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68), as well as genotypes 16 and 18 individually.
All Cause Mortality
	Cobas® 4800 HPV Test
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cobas® 4800 HPV Test
	Affected / at Risk (%)	# Events
Total	1/47208 (0%)
Vascular disorders
Urogenital haemorrhage	1/47208 (0%)
Other (Not Including Serious) Adverse Events
	Cobas® 4800 HPV Test
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.