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A Two-Stage Phase 2 Study Of Dose-Intense 4,4'-Dihydroxybenzophenone-2,4-Dinitrophenyl-Hydrazone (A-007) Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix

Phase 2
18 Years
Not Enrolling
Cervical Intraepithelial Neoplasia, Uterine Cervical Dysplasia

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Trial Information

A Two-Stage Phase 2 Study Of Dose-Intense 4,4'-Dihydroxybenzophenone-2,4-Dinitrophenyl-Hydrazone (A-007) Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix

This is a non-randomized, two-stage phase II study with pathological response rate as the
primary objective. Following biopsy confirmation of CIN 2/3 within the last 12 weeks, women
will treat themselves with gel applied to the cervix via an intravaginal applicator.
Patients will apply gel once daily for 14 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 (see schedule of events in attachment TG-003.01 for visit intervals).

Following the two cycles of treatment with A-007, treating physicians will perform a LEEP at
the month 4 visit. The investigator is responsible for ensuring that the LEEP is conducted
according to the procedures and guidelines of their institution.

Inclusion 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 histologic proof of CIN 2/3 disease documented within the last 12
weeks. If patient is enrolled using prior local biopsy, local slides and pathology
report must be sent to the central laboratory. Patient may be enrolled into the
study based on local laboratory results of CIN 2/3 and will not be discontinued if
central laboratory results differ.

- Cervical swabs must test positive for high risk HPV (by Hybrid Capture 2). If the
patient tests negative for high risk HPV and has proof of CIN 2/3, the patient should
be retested one additional time for high-risk HPV.

- Patients must have a Hgb ≥ 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 study (until performance of the LEEP at month 4): oral, implantable,
injectable contraceptives; abstinence (celibacy). Contraceptive sponges, IUD, vaginal
contraceptive rings, spermacides, sponges, condoms, or partner's vasectomy are not
acceptable methods of birth control.

Exclusion Criteria:

- Patients with CIN 1 or with invasive squamous cell carcinoma (SCC).

- CIN appearing to involve the endocervix, as assessed colposcopically

- CIN not amenable to adequate colposcopic follow-up evaluations, i.e. unsatisfactory

- CIN 3 involving more than two cervical quadrants on colposcopy.

- Patients treated for cervical SIL within the past year.

- Patients who have had a LEEP performed in the past 12 months

- Patients with other malignancy (except non-melanoma skin) within the past 5 years.

- Patients with any chronic, 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 >5 mg/d of prednisone (or its equivalent).

- Participation in another investigational medication trial concurrently or within 30
days, or prior administration of a prophylactic HPV vaccine or 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.

- Patients with known menstrual irregularity that is not resolved with cycling on
hormonal contraception.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine overall pathological response (complete and partial, based on independent review at month 4) of A-007 when applied topically for two 28-day cycles of 14 consec. days of treatment each to the uterine cervix of women with HSIL [CIN 2/3].

Outcome Time Frame:

Over the course of the trial

Safety Issue:


Principal Investigator

Keith A Aqua, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Visions Clinical Research


United States: Food and Drug Administration

Study ID:




Start Date:

November 2007

Completion Date:

August 2008

Related Keywords:

  • Cervical Intraepithelial Neoplasia
  • Uterine Cervical Dysplasia
  • 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)
  • Neoplasms
  • Uterine Cervical Dysplasia
  • Cervical Intraepithelial Neoplasia
  • Carcinoma in Situ



NYU School of MedicineNew York, New York  10016
Visions Clinical ResearchBoynton Beach, Florida  33472
Visions Clinical Research-TucsonTucson, Arizona  85712
Robin Black OGNPCosta Mesa, California  92629
Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's HealthBronx, New York  10461