Cervical Intraepithelial NeoplasiaPhase 2NCT00285207
Safety and Efficacy of A-007 Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix
A Phase 2 study testing A007 in people with Cervical Intraepithelial Neoplasia and Uterine Cervical Dysplasia, run by Tigris Pharmaceuticals at 29 sites in United States.
Trial summary
A-007 is an investigational therapy which may be effective in the treatment of pre-cancerous cervical dysplasia (abnormal cell growth). The purpose of this study is to evaluate the safety and efficacy of A-007, when used to treat high-grade cervical dysplasia. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Intraepithelial Neoplasia, Uterine Cervical Dysplasia
- What is being tested?
- A007
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 147 participants
- Where
- 29 sitesUnited States
- Study dates
- Jan 2006to Jun 2008
- Phase
- Phase 2
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients may be enrolled in the study only if they meet all of the following criteria:
- 18 years of age or older
- The patient or her authorized representative must sign and date an Ethical Review Board-approved informed consent document. All aspects of the protocol must be explained and written informed consent obtained.
- Patients must have histological proof of HSIL (CIN 2/3) disease documented.
- Cervical swabs must test positive for HPV (by Hybrid Capture 2).
- Patients must have a Hb ≥ 9 g/dl, a peripheral WBC ≥ 3000 mm3 and platelet counts ≥ 100,000 mm3.
- Normal hepatic and renal functions - AST and ALT < 2.5 x ULN and creatinine < 1.5 x ULN, respectively.
- Females of childbearing potential must use one of the following birth control methods during the treatment period and 2 weeks thereafter: oral, implantable, injectable contraceptives; abstinence (celibacy). Contraceptive sponges, IUD, spermicides, sponges, condoms, or partner's vasectomy are not acceptable methods of birth control.
Who cannot join
- Patients will be excluded from the study for any of the following preexisting reasons:
- Patients with LSIL (CIN 1) or invasive squamous cell carcinoma (SCC).
- SIL (CIN) involving the endocervix as determined by endocervical curettage, or otherwise not amenable to adequate colposcopic follow-up evaluations, i.e. unsatisfactory colposcopy.
- CIN 3 involving more than two cervical quadrants on colposcopy.
- Patients treated for cervical SIL within the past year.
- Patients with other malignancy (except for non-melanoma skin) within the past 5 years.
Show all 15Show fewer
- Patients with any active infections (including HIV) other than HPV.
- Patients with known clinically relevant immunological deficiency.
- Concurrent treatment with cytotoxic, radiation, or immuno-stimulative therapy, or with systemic corticosteroids at a dose of > 5 mg/d of prednisone (or its equivalent).
- Participation in another investigational medication trial concurrently or within 30 days, or prior participation in an HPV vaccine trial. Treatment within the last 30 days with a medication that has not received regulatory approval at the time of study entry.
- Concomitant use of topical vaginal medications.
- Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study.
- History of allergy or hypersensitivity to cosmetics, toiletries, or other topical or dermatologic products.
- Pregnant or lactating females who are nursing and will not consent to cease nursing.
- Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
Lehigh Valley Hospital
Allentown, Pennsylvania, 18102
Mount Vernon Clinical Research, LLC
Atlanta, Georgia, 30328
Medical College of Georgia
Augusta, Georgia, 30912
Hill Country OB/GYN
Austin, Texas, 78737
University of Alabama Highlands, Dept. of OB/GYN
Birmingham, Alabama, 35205
Visions Clinical Research
Boynton Beach, Florida, 33437
Northern California Research Corp
Carmichael, California, 95608
Greater Cincinnati OB/GYN, Inc.
Cincinnati, Ohio, 45267
Arrowhead Regional Medical Center
Colton, California, 92324
South Carolina Oncology Associates
Columbia, South Carolina, 29210
Robin Black OGNP
Costa Mesa, California, 92629
Planned Parenthood of Houston & Southeast Texas, Inc.
Houston, Texas, 77004
Office of R. Garn Mabey, MD
Las Vegas, Nevada, 89128
East Jefferson OB/GYN
Metairie, Louisiana, 70006
Jersey Shore University Medical Center
Neptune City, New Jersey, 07754
Coastal Connecticut Research, LLC
New London, Connecticut, 06320
New York Downtown Hospital
New York, New York, 10038
University of Oklahoma Health Sciences Center Dept of OB/GYN
Oklahoma City, Oklahoma, 73104
Global OB/GYN Centers of Florida
Pembroke Pines, Florida, 33024
Hope Research Institute, LLC
Phoenix, Arizona, 85032
Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services
Pittsburgh, Pennsylvania, 15213
4601 Old Shepard Place; Bldg 2, Suite 201
Plano, Texas, 75093
IGO Medical Group of San Diego
San Diego, California, 92121
Physician Care Clinical Research, LLC.
Sarasota, Florida, 34239
Jacobi Medical Center
The Bronx, New York, 10461
Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health
The Bronx, New York, 10461
Visions Clinical Research-Tucson
Tucson, Arizona, 85712
Washington Hospital Center
Washington D.C., District of Columbia, 20010
OB/GYN Specialists of the Palm Beaches
West Palm Beach, Florida, 33401
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Trial of the Use of 4,4'-Dihydroxybenzophenone-2,4-Dinitrophenyl-hydrazone (A-007) Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix
A-007 is an investigational therapy which may be effective in the treatment of pre-cancerous cervical dysplasia (abnormal cell growth). The purpose of this study is to evaluate the safety and efficacy of A-007, when used to treat high-grade cervical dysplasia.
Read the detailed description
This is a randomized, double-blind, placebo-controlled study. It will randomize patients in a 1:1 ratio to topical cervical treatment with A-007, or placebo gel. Following biopsy confirmation of High Grade Squamous Intraepithelial Lesions (HSIL), women will treat themselves with gel applied to the cervix via an intravaginal applicator. Patients will apply gel once daily for 5 consecutive days of a 28-day cycle for 2 cycles. Women will return to clinic for safety assessments, colposcopy, cytology, and virologic and immunologic testing.
- Being tested
- placebo, A007
- Keywords
- Cervical Intraepithelial Neoplasia (CIN), High-grade Cervical Intraepithelial Neoplasia, High-grade Squamous Intraepithelial Lesions (HSIL), Human Papilloma Virus (HPV), High-Grade Cervical Intraepithelial Lesions (CIN 2/3)
- Medical subject headings
- Uterine Cervical Dysplasia, Squamous Intraepithelial Lesions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
5 days of 28 day cycle for 2 cycles
A007Drug
5 days of 28 day cycle
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles. Receives: Drug: placebo |
| A007 | Experimental | 0.25% A007 administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles. Receives: Drug: A007 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Response
Pathological resonse is defined as a patient who regressed from Cervical intraepithelial neoplasia (CIN) 2/3 to normal at the end of 4 months.
Measured: baseline and 4 months
Secondary outcomes (3)
Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0.
Measured: over the course of the trial
Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection.
Measured: over the course of the trial
Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection.
Measured: over the course of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2006 (estimated)
- Study startJan 2006
- Primary completionApr 2008
- Study completionJun 2008
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tigris Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- John A Burigo, MD, Principal investigator, OB/GYN Specialists of the Palm BeachesRamon Cestero, MD, Principal investigator, Arrowhead Regional Medical CenterPaul M Fine, MD, Principal investigator, Planned Parenthood of Houston & Southeast Texas, Inc.Keith A Aqua, MD, Principal investigator, Visions Clinical ResearchSteven C Blank, MD, Principal investigator, Mount Vernon Clinical Research, LLCDouglas G Young, MD, Principal investigator, Northern California Research CorpAllan T Sawyer, MD, Principal investigator, Hope Research Institute, LLCMark H Einstein, MD, Principal investigator, Montefiore Medical Center-Weiler Division
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00285207
- Sponsor's protocol ID
- TG-001
- Status last verified
- Sep 2010
- First submitted
- 30 Jan 2006
- Last updated
- 11 Oct 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Morgan LR, Thangaraj K, LeBlanc B, Rodgers A, Wolford LT, Hooper CL, Fan D, Jursic BS. Design, synthesis, and anticancer properties of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues. J Med Chem. 2003 Oct 9;46(21):4552-63. doi: 10.1021/jm0301080.
PubMed 14521417Morgan, LR, Hooper, CL, Rodgers, AH, LoRusso, P, Eilender, DE and Culotta, VA. 4,4'-Dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone (A-007): A CD4+ T-Lymphocyte Modulator Useful in the Treatment of Advanced Cancer. Chemotherapy - accepted 2005.
Morgan, LR, Hooper, CL, Rodgers, AH Culotta, V et al. 4,4'-Dihydroxy benzophenone -2,4-dinitrophenylhydrazone (A-007) A Modulator of CD45+ T Lymphocytes in HPV Infected Anogenital Epithelium. In: HPV Vaccines and Immune Therapy, Cambridge, United Kingdom, 2003
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Trial of the Use of 4,4'-Dihydroxybenzophenone-2,4-Dinitrophenyl-hydrazone (A-007) Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix
- ClinicalTrials.gov ID
- NCT00285207
- Acronym / sponsor ID
- TG-001
- Keywords
- Cervical Intraepithelial Neoplasia (CIN), High-grade Cervical Intraepithelial Neoplasia, High-grade Squamous Intraepithelial Lesions (HSIL), Human Papilloma Virus (HPV), High-Grade Cervical Intraepithelial Lesions (CIN 2/3)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- Tigris PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2006
- Primary completion
- Apr 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 1 Feb 2006 (estimated)
- Results
- Posted 11 Oct 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A-007 is an investigational therapy which may be effective in the treatment of pre-cancerous cervical dysplasia (abnormal cell growth). The purpose of this study is to evaluate the safety and efficacy of A-007, when used to treat high-grade cervical dysplasia.
Detailed description
This is a randomized, double-blind, placebo-controlled study. It will randomize patients in a 1:1 ratio to topical cervical treatment with A-007, or placebo gel. Following biopsy confirmation of High Grade Squamous Intraepithelial Lesions (HSIL), women will treat themselves with gel applied to the cervix via an intravaginal applicator. Patients will apply gel once daily for 5 consecutive days of a 28-day cycle for 2 cycles. Women will return to clinic for safety assessments, colposcopy, cytology, and virologic and immunologic testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: placeboPlacebo administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles. |
| A007 | Experimental | Drug: A0070.25% A007 administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years of age or older
- The patient or her authorized representative must sign and date an Ethical Review Board-approved informed consent document. All aspects of the protocol must be explained and written informed consent obtained.
- Patients must have histological proof of HSIL (CIN 2/3) disease documented.
- Cervical swabs must test positive for HPV (by Hybrid Capture 2).
- Patients must have a Hb ≥ 9 g/dl, a peripheral WBC ≥ 3000 mm3 and platelet counts ≥ 100,000 mm3.
Key exclusion criteria (15 listed)
- Patients with LSIL (CIN 1) or invasive squamous cell carcinoma (SCC).
- SIL (CIN) involving the endocervix as determined by endocervical curettage, or otherwise not amenable to adequate colposcopic follow-up evaluations, i.e. unsatisfactory colposcopy.
- CIN 3 involving more than two cervical quadrants on colposcopy.
- Patients treated for cervical SIL within the past year.
- Patients with other malignancy (except for non-melanoma skin) within the past 5 years.
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 |
|---|---|---|
| placebo5 days of 28 day cycle for 2 cycles | Drug | Placebo |
| A0075 days of 28 day cycle | Drug | A007 |
Primary outcome
Pathological Response
Time frame: baseline and 4 months
Pathological resonse is defined as a patient who regressed from Cervical intraepithelial neoplasia (CIN) 2/3 to normal at the end of 4 months.
3 secondary outcomes
Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0.
Time frame: over the course of the trial
Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection.
Time frame: over the course of the trial
Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection.
Time frame: over the course of the trial
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 14521417Morgan LR, Thangaraj K, LeBlanc B, Rodgers A, Wolford LT, Hooper CL, Fan D, Jursic BS. Design, synthesis, and anticancer properties of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues. J Med Chem. 2003 Oct 9;46(21):4552-63. doi: 10.1021/jm0301080.
- BackgroundMorgan, LR, Hooper, CL, Rodgers, AH, LoRusso, P, Eilender, DE and Culotta, VA. 4,4'-Dihydroxybenzophenone-2,4-dinitrophenyl-hydrazone (A-007): A CD4+ T-Lymphocyte Modulator Useful in the Treatment of Advanced Cancer. Chemotherapy - accepted 2005.
- BackgroundMorgan, LR, Hooper, CL, Rodgers, AH Culotta, V et al. 4,4'-Dihydroxy benzophenone -2,4-dinitrophenylhydrazone (A-007) A Modulator of CD45+ T Lymphocytes in HPV Infected Anogenital Epithelium. In: HPV Vaccines and Immune Therapy, Cambridge, United Kingdom, 2003
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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.
John A Burigo, MD principal investigator
OB/GYN Specialists of the Palm Beaches
Ramon Cestero, MD principal investigator
Arrowhead Regional Medical Center
Paul M Fine, MD principal investigator
Planned Parenthood of Houston & Southeast Texas, Inc.
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing A007 in people with Cervical Intraepithelial Neoplasia and Uterine Cervical Dysplasia, run by Tigris Pharmaceuticals at 29 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 8 inclusion and 15 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 11 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 11 Oct 2010). 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?
Pathological Response (time frame: baseline and 4 months). 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 NCT00285207, 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 11 Oct 2010.