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Safety and Efficacy of A-007 Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix

This study has been completed.
Sponsor:
Information provided by:
Tigris Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00285207
First received: January 30, 2006
Last updated: September 23, 2010
Last verified: September 2010
  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: placebo
Drug: A007
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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:
  • Pathological Response [ Time Frame: baseline and 4 months ] [ Designated as safety issue: No ]
    Pathological resonse is defined as a patient who regressed from Cervical intraepithelial neoplasia (CIN) 2/3 to normal at the end of 4 months.


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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection. [ Time Frame: over the course of the trial ] [ Designated as safety issue: No ]

Enrollment: 147
Study Start Date: January 2006
Study Completion Date: June 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles.
Drug: placebo
5 days of 28 day cycle for 2 cycles
Other Name: placebo
Experimental: A007
0.25% A007 administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles.
Drug: A007
5 days of 28 day cycle
Other Name: A007

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.

  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 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.

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
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: NCT00285207

  Hide Study Locations
Locations
United States, Alabama
University of Alabama Highlands, Dept. of OB/GYN
Birmingham, Alabama, United States, 35205
United States, Arizona
Hope Research Institute, LLC
Phoenix, Arizona, United States, 85032
Visions Clinical Research-Tucson
Tucson, Arizona, United States, 85712
United States, California
Northern California Research Corp
Carmichael, California, United States, 95608
Arrowhead Regional Medical Center
Colton, California, United States, 92324
Robin Black OGNP
Costa Mesa, California, United States, 92629
IGO Medical Group of San Diego
San Diego, California, United States, 92121
United States, Connecticut
Coastal Connecticut Research, LLC
New London, Connecticut, United States, 06320
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Florida
Visions Clinical Research
Boynton Beach, Florida, United States, 33437
Global OB/GYN Centers of Florida
Pembroke Pines, Florida, United States, 33024
Physician Care Clinical Research, LLC.
Sarasota, Florida, United States, 34239
OB/GYN Specialists of the Palm Beaches
West Palm Beach, Florida, United States, 33401
United States, Georgia
Mount Vernon Clinical Research, LLC
Atlanta, Georgia, United States, 30328
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Louisiana
East Jefferson OB/GYN
Metairie, Louisiana, United States, 70006
United States, Nevada
Office of R. Garn Mabey, MD
Las Vegas, Nevada, United States, 89128
United States, New Jersey
Jersey Shore University Medical Center
Neptune, New Jersey, United States, 07754
United States, New York
Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health
Bronx, New York, United States, 10461
Jacobi Medical Center
Bronx, New York, United States, 10461
New York Downtown Hospital
New York, New York, United States, 10038
United States, Ohio
Greater Cincinnati OB/GYN, Inc.
Cincinnati, Ohio, United States, 45267
United States, Oklahoma
University of Oklahoma Health Sciences Center Dept of OB/GYN
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Lehigh Valley Hospital
Allentown, Pennsylvania, United States, 18102
Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
South Carolina Oncology Associates
Columbia, South Carolina, United States, 29210
United States, Texas
Hill Country OB/GYN
Austin, Texas, United States, 78737
Planned Parenthood of Houston & Southeast Texas, Inc.
Houston, Texas, United States, 77004
4601 Old Shepard Place; Bldg 2, Suite 201
Plano, Texas, United States, 75093
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 Georgia Regents University
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, 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: Chief Medical Officer, Tigris
ClinicalTrials.gov Identifier: NCT00285207     History of Changes
Other Study ID Numbers: TG-001
Study First Received: January 30, 2006
Results First Received: August 30, 2010
Last Updated: September 23, 2010
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:
Carcinoma in Situ
Cervical Intraepithelial Neoplasia
Neoplasms
Uterine Cervical Dysplasia
Carcinoma
Genital Diseases, Female
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Precancerous Conditions
Uterine Cervical Diseases
Uterine Diseases

ClinicalTrials.gov processed this record on November 20, 2014