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

NCT ID: NCT00285207

Last Updated: 2010-10-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2008-06-30

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.

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.

Conditions

Cervical Intraepithelial Neoplasia; Uterine Cervical Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

5 days of 28 day cycle for 2 cycles

A007

0.25% A007 administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles.

Group Type: EXPERIMENTAL

A007

Intervention Type: DRUG

5 days of 28 day cycle

Interventions

placebo

5 days of 28 day cycle for 2 cycles

Intervention Type: DRUG

A007

5 days of 28 day cycle

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Tigris Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Tigris

Principal Investigators

John A Burigo, MD

Role: PRINCIPAL_INVESTIGATOR

OB/GYN Specialists of the Palm Beaches

Ramon Cestero, MD

Role: PRINCIPAL_INVESTIGATOR

Arrowhead Regional Medical Center

Paul M Fine, MD

Role: PRINCIPAL_INVESTIGATOR

Planned Parenthood of Houston & Southeast Texas, Inc.

Keith A Aqua, MD

Role: PRINCIPAL_INVESTIGATOR

Visions Clinical Research

Steven C Blank, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Vernon Clinical Research, LLC

Douglas G Young, MD

Role: PRINCIPAL_INVESTIGATOR

Northern California Research Corp

Allan T Sawyer, MD

Role: PRINCIPAL_INVESTIGATOR

Hope Research Institute, LLC

Mark H Einstein, MD

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center-Weiler Division

Robert M Spitz, MD

Role: PRINCIPAL_INVESTIGATOR

Coastal Connecticut Research, LLC

Thomas A deHoop, MD

Role: PRINCIPAL_INVESTIGATOR

Greater Cincinnati OB/GYN, Inc.

Lance R Bruck, MD

Role: PRINCIPAL_INVESTIGATOR

Jacobi Medical Center

Warner K Huh, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama Highlands, Dept. of OB/GYN

Giuseppe Del Priore, MD

Role: PRINCIPAL_INVESTIGATOR

New York Presbyterian Hospital

Michael A Gold, MD

Role: PRINCIPAL_INVESTIGATOR

University of Oklahoma Health Sciences Center Dept of OB/GYN

Richard S Guido, MD

Role: PRINCIPAL_INVESTIGATOR

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

Philip E Young, MD

Role: PRINCIPAL_INVESTIGATOR

IGO Medical Group of San Diego

Daron G. Ferris, MD

Role: PRINCIPAL_INVESTIGATOR

Augusta University

Cynthia J Goldberg, MD

Role: PRINCIPAL_INVESTIGATOR

Visions Clinical Research-Tucson

Ana Eduardo, MD

Role: PRINCIPAL_INVESTIGATOR

Hill Country OB/GYN

Phyllis Gee, MD

Role: PRINCIPAL_INVESTIGATOR

OB/GYN

Robert Pfeffer, MD

Role: PRINCIPAL_INVESTIGATOR

Robin Black OGNP, Costa Mesa California

Jonathan A Cosin, MD

Role: PRINCIPAL_INVESTIGATOR

Medstar Health Research Institute

James A Williams, MD

Role: PRINCIPAL_INVESTIGATOR

South Carolina Oncology Associates

Vincent A Culotta, Jr, MD

Role: PRINCIPAL_INVESTIGATOR

East Jefferson OB/GYN

G. Michael Swor, MD

Role: PRINCIPAL_INVESTIGATOR

Physician Care Clinical Research, LLC.

Garn R Mabey, MD

Role: PRINCIPAL_INVESTIGATOR

Office of R. Garn Mabey, MD

Martin Martino, MD

Role: PRINCIPAL_INVESTIGATOR

Lehigh Valley Hospital

Robert Klein, MD

Role: PRINCIPAL_INVESTIGATOR

Global OB/GYN Centers of Florida

William J Mann, MD

Role: PRINCIPAL_INVESTIGATOR

Jersey Shore University Medical Center

Locations

University of Alabama Highlands, Dept. of OB/GYN

Birmingham, Alabama, United States

Hope Research Institute, LLC

Phoenix, Arizona, United States

Visions Clinical Research-Tucson

Tucson, Arizona, United States

Northern California Research Corp

Carmichael, California, United States

Arrowhead Regional Medical Center

Colton, California, United States

Robin Black OGNP

Costa Mesa, California, United States

IGO Medical Group of San Diego

San Diego, California, United States

Coastal Connecticut Research, LLC

New London, Connecticut, United States

Washington Hospital Center

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

Visions Clinical Research

Boynton Beach, Florida, United States

Global OB/GYN Centers of Florida

Pembroke Pines, Florida, United States

Physician Care Clinical Research, LLC.

Sarasota, Florida, United States

OB/GYN Specialists of the Palm Beaches

West Palm Beach, Florida, United States

Mount Vernon Clinical Research, LLC

Atlanta, Georgia, United States

Medical College of Georgia

Augusta, Georgia, United States

East Jefferson OB/GYN

Metairie, Louisiana, United States

Office of R. Garn Mabey, MD

Las Vegas, Nevada, United States

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

New York Downtown Hospital

New York, New York, United States

Jacobi Medical Center

The Bronx, New York, United States

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

The Bronx, New York, United States

Greater Cincinnati OB/GYN, Inc.

Cincinnati, Ohio, United States

University of Oklahoma Health Sciences Center Dept of OB/GYN

Oklahoma City, Oklahoma, United States

Lehigh Valley Hospital

Allentown, Pennsylvania, United States

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

Pittsburgh, Pennsylvania, United States

South Carolina Oncology Associates

Columbia, South Carolina, United States

Hill Country OB/GYN

Austin, Texas, United States

Planned Parenthood of Houston & Southeast Texas, Inc.

Houston, Texas, United States

4601 Old Shepard Place; Bldg 2, Suite 201

Plano, Texas, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 14521417 (View on PubMed)

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.

Reference Type: 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

Reference Type: BACKGROUND

Other Identifiers

TG-001

Identifier Type: -

Identifier Source: org_study_id