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Safety and Efficacy Trial of the Use of A-007 Topical Gel in the Treatment of HSIL of the Cervix
This study has been completed.
First Received: January 30, 2006   Last Updated: June 18, 2008   History of Changes
Sponsored by: Tigris Pharmaceuticals
Information provided by: Tigris Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00285207
  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 II

Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy 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

Resource links provided by NLM:


Further study details as provided by Tigris Pharmaceuticals:

Primary Outcome Measures:
  • To determine the pathological response (based on independent pathology review at month 4) of A-007 as compared to placebo, to the uterine cervix of women with HSIL [CIN 2/3] [ Time Frame: over the course of the trial ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 212
Study Start Date: January 2006
Study Completion Date: June 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
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 HSIL (CIN 2/3), 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.

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 his/her institution.

  Eligibility

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

Inclusion Criteria:

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 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 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.

Exclusion Criteria:

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.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00285207

  Show 29 Study Locations
Sponsors and Collaborators
Tigris Pharmaceuticals
Investigators
Principal Investigator: John A Burigo, MD OB/GYN Specialists of the Palm Beaches
Principal Investigator: Ramon Cestero, MD Arrowhead Regional Medical Center
Principal Investigator: Paul M Fine, MD Planned Parenthood of Houston & Southeast Texas, Inc.
Principal Investigator: Keith A Aqua, MD Visions Clinical Research
Principal Investigator: Steven C Blank, MD Mount Vernon Clinical Research, LLC
Principal Investigator: Douglas G Young, MD Northern California Research Corp
Principal Investigator: Allan T Sawyer, MD Hope Research Institute, LLC
Principal Investigator: Mark H Einstein, MD Montefiore Medical Center-Weiler Division
Principal Investigator: Robert M Spitz, MD Coastal Connecticut Research, LLC
Principal Investigator: Thomas A deHoop, MD Greater Cincinnati OB/GYN, Inc.
Principal Investigator: Lance R Bruck, MD Jacobi Medical Center
Principal Investigator: Warner K Huh, MD University of Alabama Highlands, Dept. of OB/GYN
Principal Investigator: Giuseppe Del Priore, MD New York Downtown Hospital
Principal Investigator: Michael A Gold, MD University of Oklahoma Health Sciences Center Dept of OB/GYN
Principal Investigator: Richard S Guido, MD Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services
Principal Investigator: Philip E Young, MD IGO Medical Group of San Diego
Principal Investigator: Daron G. Ferris, MD Medical College of Georgia
Principal Investigator: Cynthia J Goldberg, MD Visions Clinical Research-Tucson
Principal Investigator: Ana Eduardo, MD Hill Country OB/GYN
Principal Investigator: Phyllis Gee, MD OB/GYN
Principal Investigator: Robert Pfeffer, MD Robin Black OGNP, Costa Mesa California
Principal Investigator: Jonathan A Cosin, MD Washington Hospital Center
Principal Investigator: James A Williams, MD South Carolina Oncology Associates
Principal Investigator: Vincent A Culotta, Jr, MD East Jefferson OB/GYN
Principal Investigator: G. Michael Swor, MD Physician Care Clinical Research, LLC.
Principal Investigator: Garn R Mabey, MD Office of R. Garn Mabey, MD
Principal Investigator: Martin Martino, MD Lehigh Valley Hospital
Principal Investigator: Robert Klein, MD Global OB/GYN Centers of Florida
Principal Investigator: William J Mann, MD JERSEY SHORE UNIVERSITY MEDICAL CENTER
  More Information

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.
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 ID Numbers: TG-001
Study First Received: January 30, 2006
Last Updated: June 18, 2008
ClinicalTrials.gov Identifier: NCT00285207     History of Changes
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)

Study placed in the following topic categories:
Genital Diseases, Female
Virus Diseases
Uterine Cervical Diseases
Precancerous Conditions
Carcinoma in Situ
Uterine Diseases
Papilloma
Uterine Cervical Dysplasia
Neoplasms, Glandular and Epithelial
Carcinoma
Cervical Intraepithelial Neoplasia

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

ClinicalTrials.gov processed this record on August 30, 2009