A Two-Stage Phase 2 Study Of A-007 Topical Gel in High-Grade Squamous Intraepithelial Lesions (HSIL) (TG-003)

This study has been completed.
Sponsor:
Information provided by:
Tigris Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00596258
First received: January 4, 2008
Last updated: May 21, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Cervical Intraepithelial Neoplasia
Uterine Cervical Dysplasia
Drug: A-007
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Tigris Pharmaceuticals:

Primary Outcome Measures:
  • 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]. [ Time Frame: Over the course of the trial ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine the local tolerability and systemic safety of A-007. [ Time Frame: over the course of the trial ] [ Designated as safety issue: Yes ]
  • Evaluate the effects of A-007 gel treatment on human papillomavirus (HPV) eradication. [ Time Frame: over the course of the trial ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: November 2007
Study Completion Date: August 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A-007
Single arm open label
Drug: A-007
applied topically for two 28-day cycles of 14 consecutive days of treatment each to the uterine cervix

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 colposcopy.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00596258

Locations
United States, Arizona
Visions Clinical Research-Tucson
Tucson, Arizona, United States, 85712
United States, California
Robin Black OGNP
Costa Mesa, California, United States, 92629
United States, Florida
Visions Clinical Research
Boynton Beach, Florida, United States, 33437
United States, New York
Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health
Bronx, New York, United States, 10461
NYU School of Medicine
New York, New York, United States, 10016
Sponsors and Collaborators
Tigris Pharmaceuticals
Investigators
Principal Investigator: Keith A Aqua, MD Visions Clinical Research
Principal Investigator: Mark H Einstein, MD Montefiore Medical Center-Weiler Division
Principal Investigator: Cynthia J Goldberg, MD Visions Clinical Research-Tucson
Principal Investigator: Robert Pfeffer, MD Robin Black OGNP, Costa Mesa California
Principal Investigator: Stephanie Blank, MD NYU School of Medicine
  More Information

Publications:
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

Responsible Party: Anne White, Tigris Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00596258     History of Changes
Other Study ID Numbers: TG-003
Study First Received: January 4, 2008
Last Updated: May 21, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Tigris Pharmaceuticals:
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)

Additional relevant MeSH terms:
Neoplasms
Cervical Intraepithelial Neoplasia
Carcinoma in Situ
Uterine Cervical Dysplasia
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Precancerous Conditions
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on September 30, 2014