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

Cervical Intraepithelial Neoplasia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00285207
• Other study ID #: TG-001
• Status: Completed
• Phase: Phase 2
• First received: January 30, 2006
• Last updated: September 23, 2010
• Start date: January 2006
• Est. completion date: June 2008

Study information

• Verified date: September 2010
• Source: Tigris Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: June 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma in Situ
• Cervical Intraepithelial Neoplasia
• Uterine Cervical Dysplasia

Intervention

Drug:
• placebo
5 days of 28 day cycle for 2 cycles
• A007
5 days of 28 day cycle

Locations

Country	Name	City	State
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Mount Vernon Clinical Research, LLC	Atlanta	Georgia
United States	Medical College of Georgia	Augusta	Georgia
United States	Hill Country OB/GYN	Austin	Texas
United States	University of Alabama Highlands, Dept. of OB/GYN	Birmingham	Alabama
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health	Bronx	New York
United States	Northern California Research Corp	Carmichael	California
United States	Greater Cincinnati OB/GYN, Inc.	Cincinnati	Ohio
United States	Arrowhead Regional Medical Center	Colton	California
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	Robin Black OGNP	Costa Mesa	California
United States	Planned Parenthood of Houston & Southeast Texas, Inc.	Houston	Texas
United States	Office of R. Garn Mabey, MD	Las Vegas	Nevada
United States	East Jefferson OB/GYN	Metairie	Louisiana
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Coastal Connecticut Research, LLC	New London	Connecticut
United States	New York Downtown Hospital	New York	New York
United States	University of Oklahoma Health Sciences Center Dept of OB/GYN	Oklahoma City	Oklahoma
United States	Global OB/GYN Centers of Florida	Pembroke Pines	Florida
United States	Hope Research Institute, LLC	Phoenix	Arizona
United States	Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services	Pittsburgh	Pennsylvania
United States	4601 Old Shepard Place; Bldg 2, Suite 201	Plano	Texas
United States	IGO Medical Group of San Diego	San Diego	California
United States	Physician Care Clinical Research, LLC.	Sarasota	Florida
United States	Visions Clinical Research-Tucson	Tucson	Arizona
United States	Washington Hospital Center	Washington	District of Columbia
United States	OB/GYN Specialists of the Palm Beaches	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Tigris Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0.		over the course of the trial	No
Secondary	Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection.		over the course of the trial	No
Secondary	Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection.		over the course of the trial	No