Cervical Intraepithelial NeoplasiaPhase 3NCT01131312
Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS)
A Phase 3 study testing Thinprep, Hybrid capture 2 and Colposcopy in people with Cervical Intraepithelial Neoplasia, run by National Cancer Institute (NCI) at 3 sites in United States.
Trial summary
Approximately 65 million Pap smears are performed each year in the United States. The vast majority of results are negative (no abnormality identified) but about 5 percent to 8 percent are reported as abnormal. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia
- What is being tested?
- Thinprep, Hybrid capture 2 and Colposcopy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5,060 participants
- Where
- 3 sitesUnited States
- Study dates
- 20 Feb 2008to 5 Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL)
- 18 years or older
- Able to give informed consent with reasonable likelihood of follow-up
Who cannot join
- Previous Hysterectomy
- History of excisional or ablative treatment of cervix, such as laser treatment, radiation therapy, cauterization (burning), freezing or surgery such as cone biopsy or loop electrosurgical excision procedure (LEEP).
- Already known to be pregnant
- Already known to be human immunodeficiency virus (HIV) positive (HIV may negatively affect the clinical history of human papillomavirus (HPV), making triage less appropriate.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Oklahoma
Oklahoma City, Oklahoma, 73019
Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213
University of Washington
Seattle, Washington, 98195
About this study
Approximately 65 million Pap smears are performed each year in the United States. The vast majority of results are negative (no abnormality identified) but about 5 percent to 8 percent are reported as abnormal. Most low-grade changes regress spontaneously; only a minority of such lesions would progress to a cancer precursor without treatment. However, there is no way to determine morphologically which patients are at risk or progression. Therefore, both high- and low-grade lesions were often managed with colposcopy and directed biopsy.
Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the Atypical squamous cells of undetermined significance (ASCUS)- Low grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) trial was to use the information we have gained about the role of HPV to design better treatment and prevention strategies to reduce the burden of cervical cancer and its precursors.
Read more
ALTS consisted of three management strategies: (1) immediate colposcopy of all women; (2) repeat cytology with colposcopy only if the results show a high grade lesion; and (3) HPV testing and repeat cytology in combination, with referral to colposcopy if either the HPV test is positive or the cytology shows a high grade lesion. Four Clinical Centers University of Alabama, Birmingham Alabama (AL); Magee-Womens Hospital, Pittsburgh Pennsylvania (PA); University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle Washington (WA) enrolled approximately 5,000 women with recent diagnosis of ASCUS or LSIL. Participants were followed at six month intervals for a total of 2 years.
The ALTS database and ALTS specimens continue to be a valuable research resource in studies of cervical cancer precursors, screening tests, visual assessment of the cervix and investigation of biomarkers.
Read the detailed description
Approximately 65 million Pap smears are performed each year in the United States. The vast majority of results are negative (no abnormality identified) but about 5 percent to 8 percent are reported as abnormal. Most low-grade changes regress spontaneously; only a minority of such lesions would progress to a cancer precursor without treatment. However, there is no way to determine morphologically which patients are at risk of progression. Therefore, both high- and low-grade lesions were often managed with colposcopy and directed biopsy. It was anticipated that determining alternative management strategies would yield important potential benefits including fewer medical complications from over treatment, reduced patient anxiety associated with referral for cytologic abnormalities, as well as cost savings.
Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the ALTS trial was to use the information we have gained about the role of HPV to design better treatment and prevention strategies to reduce the burden of cervical cancer and its precursors.
ALTS consisted of three management strategies: (1) immediate colposcopy of all women; (2) repeat cytology with colposcopy only if the results show a high grade lesion; and (3) HPV testing and repeat cytology in combination, with referral to colposcopy if either the HPV test is positive or the cytology shows a high grade lesion. Four Clinical Centers University of Alabama, Birmingham AL; Magee-Womens Hospital, Pittsburgh PA; University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle WA - enrolled approximately 5,000 women with recent diagnosis of ASCUS or LSIL. Participants were followed at six month intervals for a total of 2 years. The main results from ALTS showed that for women with ASCUS cytology, HPV triage was at least as safe as universal immediate colposcopy in the detection of high-grade lesion and would allow approximately half of women to return to routine follow up without additional procedures (colposcopy). No efficient triage strategy was identified for women with LSIL cytology.
The ALTS database and ALTS specimens continue to be a valuable research resource in studies of cervical cancer precursors, screening tests, visual assessment of the cervix and investigation of biomarkers.
- Conditions
- Cervical Intraepithelial Neoplasia
- Being tested
- Thinprep, Hybrid capture 2, Colposcopy
- Keywords
- Cervix, CIN, HPV, Triage, ASCUS/LSIL, Pap Smear, HPV Test
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThinprepDevice
Pap test
Hybrid capture 2Device
Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Test
ColposcopyProcedure or surgery
Procedure performed by a healthcare practitioner to examine the cervix, vagina, and vulva.
| Study group | Role | What they receive |
|---|---|---|
| Cytology | Experimental | Referred to colposcopy if cytology is high grade Receives: Device: Thinprep |
| Human Papillomavirus (HPV) | Experimental | Referred to colposcopy if cytology is high grade or HPV + Receives: Device: Hybrid capture 2 |
| Colposcopy | Experimental | All refer to colposcopy Receives: Procedure: Colposcopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Cervical Intraepithelial Neoplasia III (CIN III)
A cervical exam, pap test, human papilloma virus (HPV) deoxyribonucleic acid (DNA) test, and/or colposcopy was performed to detect whether or not a participant had CINIII. CINIII is defined as moderate or severe dysplasia or abnormal cells located on the cervix that can lead to cancer.
Measured: up to 2 years
Secondary outcomes (1)
Percentage of Participants With Cumulative Detection of Clinical Center Histologically Confirmed Cervical Intraepithelial Neoplasia 2 (CIN2) and Above (High Grade Lesion) Over the 2 Years of the Trial.
Cumulative detection of CIN2 and above was assessed by pathologists who reviewed specimens from cervical pelvic exams (i.e. thin prep pap test, Human papillomavirus (HPV) Deoxyribonucleic acid (DNA) test, and/or colposcopy). Pathologists graded the specimens from CIN2 (moderate grade lesion) to CIN3 (high grade lesion).
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2010 (estimated)
- Study start20 Feb 2008
- Primary completion5 Feb 2009
- Study completion5 Feb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cervical Intraepithelial NeoplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 5,060 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Mark Schiffman, M.D., National Institutes of Health Clinical Center (CC)
- Investigators
- Mark H Schiffman, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01131312
- Sponsor's protocol ID
- 999908076
- Other IDs
- 08-C-N076
- Status last verified
- Oct 2018
- First submitted
- 25 May 2010
- Last updated
- 20 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: The only data sharing is in cervical images which are included as a part of a larger IRB approved release to collaborators completing a data sharing agreement that prohibits re-sharing of data images. The images are shared with limited test results, metadata, and age. The images are saved in encrypted files and shared under individual password protection. Images will only be shared with bonafide researchers who are verified and complete a pilot.
Publications
Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984 May;3(5):1151-7. doi: 10.1002/j.1460-2075.1984.tb01944.x.
PubMed 6329740Cox JT, Lorincz AT, Schiffman MH, Sherman ME, Cullen A, Kurman RJ. Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 1995 Mar;172(3):946-54. doi: 10.1016/0002-9378(95)90026-8.
PubMed 7892889Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934-7. doi: 10.1126/science.2537532.
PubMed 2537532
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial on Clinical Management of ASCUS and LSIL (ALTS)
- ClinicalTrials.gov ID
- NCT01131312
- Acronym / sponsor ID
- 999908076
- Conditions
- Cervical Intraepithelial Neoplasia
- Keywords
- Cervix, CIN, HPV, Triage, ASCUS/LSIL, Pap Smear, HPV Test
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,060 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 20 Feb 2008 (actual)
- Primary completion
- 5 Feb 2009 (actual)
- Study completion
- 5 Feb 2009 (actual)
- First posted
- 26 May 2010 (estimated)
- Results
- Posted 20 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 65 million Pap smears are performed each year in the United States. The vast majority of results are negative (no abnormality identified) but about 5 percent to 8 percent are reported as abnormal. Most low-grade changes regress spontaneously; only a minority of such lesions would progress to a cancer precursor without treatment. However, there is no way to determine morphologically which patients are at risk or progression. Therefore, both high- and low-grade lesions were often managed with colposcopy and directed biopsy.
Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the Atypical squamous cells of undetermined significance (ASCUS)- Low grade squamous intraepithelial lesion (LSIL) Triage Study (ALTS) trial was to use the information we have gained about the role of HPV to design better treatment and prevention strategies to reduce the burden of cervical cancer and its precursors.
ALTS consisted of three management strategies: (1) immediate colposcopy of all women; (2) repeat cytology with colposcopy only if the results show a high grade lesion; and (3) HPV testing and repeat cytology in combination, with referral to colposcopy if either the HPV test is positive or the cytology shows a high grade lesion. Four Clinical Centers University of Alabama, Birmingham Alabama (AL); Magee-Womens Hospital, Pittsburgh Pennsylvania (PA); University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle Washington (WA) enrolled approximately 5,000 women with recent diagnosis of ASCUS or LSIL. Participants were followed at six month intervals for a total of 2 years.
The ALTS database and ALTS specimens continue to be a valuable research resource in studies of cervical cancer precursors, screening tests, visual assessment of the cervix and investigation of biomarkers.
Detailed description
Approximately 65 million Pap smears are performed each year in the United States. The vast majority of results are negative (no abnormality identified) but about 5 percent to 8 percent are reported as abnormal. Most low-grade changes regress spontaneously; only a minority of such lesions would progress to a cancer precursor without treatment. However, there is no way to determine morphologically which patients are at risk of progression. Therefore, both high- and low-grade lesions were often managed with colposcopy and directed biopsy. It was anticipated that determining alternative management strategies would yield important potential benefits including fewer medical complications from over treatment, reduced patient anxiety associated with referral for cytologic abnormalities, as well as cost savings.
Epidemiologic, virologic and molecular studies have clearly demonstrated that human papillomavirus (HPV) is the central cause of cervical cancer. The motivation for the ALTS trial was to use the information we have gained about the role of HPV to design better treatment and prevention strategies to reduce the burden of cervical cancer and its precursors.
ALTS consisted of three management strategies: (1) immediate colposcopy of all women; (2) repeat cytology with colposcopy only if the results show a high grade lesion; and (3) HPV testing and repeat cytology in combination, with referral to colposcopy if either the HPV test is positive or the cytology shows a high grade lesion. Four Clinical Centers University of Alabama, Birmingham AL; Magee-Womens Hospital, Pittsburgh PA; University of Oklahoma, Oklahoma City OK; and University of Washington, Seattle WA - enrolled approximately 5,000 women with recent diagnosis of ASCUS or LSIL. Participants were followed at six month intervals for a total of 2 years. The main results from ALTS showed that for women with ASCUS cytology, HPV triage was at least as safe as universal immediate colposcopy in the detection of high-grade lesion and would allow approximately half of women to return to routine follow up without additional procedures (colposcopy). No efficient triage strategy was identified for women with LSIL cytology.
The ALTS database and ALTS specimens continue to be a valuable research resource in studies of cervical cancer precursors, screening tests, visual assessment of the cervix and investigation of biomarkers.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cytology | Experimental | Device: ThinprepReferred to colposcopy if cytology is high grade |
| Human Papillomavirus (HPV) | Experimental | Device: Hybrid capture 2Referred to colposcopy if cytology is high grade or HPV + |
| Colposcopy | Experimental | Procedure: ColposcopyAll refer to colposcopy |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
Key exclusion criteria (4 listed)
- Previous Hysterectomy
- History of excisional or ablative treatment of cervix, such as laser treatment, radiation therapy, cauterization (burning), freezing or surgery such as cone biopsy or loop electrosurgical excision procedure (LEEP).
- Already known to be pregnant
- Already known to be human immunodeficiency virus (HIV) positive (HIV may negatively affect the clinical history of human papillomavirus (HPV), making triage less appropriate.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ThinprepPap test | Device | Cytology |
| Hybrid capture 2Human Papillomavirus (HPV) Deoxyribonucleic Acid (DNA) Test | Device | Human Papillomavirus (HPV) |
| ColposcopyProcedure performed by a healthcare practitioner to examine the cervix, vagina, and vulva. | Procedure or surgery | Colposcopy |
Primary outcome
Percentage of Participants With Cervical Intraepithelial Neoplasia III (CIN III)
Time frame: up to 2 years
A cervical exam, pap test, human papilloma virus (HPV) deoxyribonucleic acid (DNA) test, and/or colposcopy was performed to detect whether or not a participant had CINIII. CINIII is defined as moderate or severe dysplasia or abnormal cells located on the cervix that can lead to cancer.
1 secondary outcome
Percentage of Participants With Cumulative Detection of Clinical Center Histologically Confirmed Cervical Intraepithelial Neoplasia 2 (CIN2) and Above (High Grade Lesion) Over the 2 Years of the Trial.
Time frame: up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 6329740Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 1984 May;3(5):1151-7. doi: 10.1002/j.1460-2075.1984.tb01944.x.
- Background: PubMed 7892889Cox JT, Lorincz AT, Schiffman MH, Sherman ME, Cullen A, Kurman RJ. Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance. Am J Obstet Gynecol. 1995 Mar;172(3):946-54. doi: 10.1016/0002-9378(95)90026-8.
- Background: PubMed 2537532Dyson N, Howley PM, Munger K, Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science. 1989 Feb 17;243(4893):934-7. doi: 10.1126/science.2537532.
- Individual participant dataSharing planned: Yes. The only data sharing is in cervical images which are included as a part of a larger IRB approved release to collaborators completing a data sharing agreement that prohibits re-sharing of data images. The images are shared with limited test results, metadata, and age. The images are saved in encrypted files and shared under individual password protection. Images will only be shared with bonafide researchers who are verified and complete a pilot.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark H Schiffman, M.D. principal investigator
National Cancer Institute (NCI)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Thinprep, Hybrid capture 2 and Colposcopy in people with Cervical Intraepithelial Neoplasia, run by National Cancer Institute (NCI) at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Cervical Intraepithelial Neoplasia III (CIN III) (time frame: up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01131312, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2018.