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

NCT00285207 | Completed Phase 2 Results

• 1 other identifier: TG-001
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 29

Brief 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.

Conditions

Cervical Intraepithelial Neoplasia; Uterine Cervical Dysplasia

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)

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline and 4 months

Secondary Outcomes (3)

• Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0.

  over the course of the trial

• Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection.

  over the course of the trial

• Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection.

  over the course of the trial

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles.

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.

Drug: A007

Interventions

placebo DRUG

5 days of 28 day cycle for 2 cycles

Placebo

A007 DRUG

5 days of 28 day cycle

A007

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients may be enrolled in the study only if they meet all of the following criteria:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tigris Pharmaceuticals: lead

Study Sites (29)

University of Alabama Highlands, Dept. of OB/GYN

Birmingham, Alabama, 35205, United States

Location

Hope Research Institute, LLC

Phoenix, Arizona, 85032, United States

Location

Visions Clinical Research-Tucson

Tucson, Arizona, 85712, United States

Location

Northern California Research Corp

Carmichael, California, 95608, United States

Location

Arrowhead Regional Medical Center

Colton, California, 92324, United States

Location

Robin Black OGNP

Costa Mesa, California, 92629, United States

Location

IGO Medical Group of San Diego

San Diego, California, 92121, United States

Location

Coastal Connecticut Research, LLC

New London, Connecticut, 06320, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Visions Clinical Research

Boynton Beach, Florida, 33437, United States

Location

Global OB/GYN Centers of Florida

Pembroke Pines, Florida, 33024, United States

Location

Physician Care Clinical Research, LLC.

Sarasota, Florida, 34239, United States

Location

OB/GYN Specialists of the Palm Beaches

West Palm Beach, Florida, 33401, United States

Location

Mount Vernon Clinical Research, LLC

Atlanta, Georgia, 30328, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

East Jefferson OB/GYN

Metairie, Louisiana, 70006, United States

Location

Office of R. Garn Mabey, MD

Las Vegas, Nevada, 89128, United States

Location

Jersey Shore University Medical Center

Neptune City, New Jersey, 07754, United States

Location

New York Downtown Hospital

New York, New York, 10038, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health

The Bronx, New York, 10461, United States

Location

Greater Cincinnati OB/GYN, Inc.

Cincinnati, Ohio, 45267, United States

Location

University of Oklahoma Health Sciences Center Dept of OB/GYN

Oklahoma City, Oklahoma, 73104, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18102, United States

Location

Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services

Pittsburgh, Pennsylvania, 15213, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

Hill Country OB/GYN

Austin, Texas, 78737, United States

Location

Planned Parenthood of Houston & Southeast Texas, Inc.

Houston, Texas, 77004, United States

Location

4601 Old Shepard Place; Bldg 2, Suite 201

Plano, Texas, 75093, United States

Location

Related Publications (3)

• 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.

  PMID: 14521417 BACKGROUND

• Morgan, 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.

  BACKGROUND

• 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

  BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Squamous Intraepithelial Lesions

Interventions

4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: TigrisPharmaceuticals

info@tigrispharma.com

Study Officials

• 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 Presbyterian 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

  Augusta 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

  Medstar Health Research Institute

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 30, 2006
• First Posted: February 1, 2006
• Study Start: January 1, 2006
• Primary Completion: April 1, 2008
• Study Completion: June 1, 2008
• Last Updated: October 11, 2010
• Results First Posted: October 11, 2010

Record last verified: 2010-09

Locations

US (29)