Clinical trial NCT00285207: Safety and Efficacy of A-007 Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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)
Lead sponsor: Tigris Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2006-02-01
Enrollment: 147
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Pathological Response
timeFrame: baseline and 4 months
Secondary outcomes:
measure: Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0.
timeFrame: over the course of the trial
measure: Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection.
timeFrame: over the course of the trial
measure: Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection.
timeFrame: over the course of the trial
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Highlands, Dept. of OB/GYN
state: Alabama
city: Phoenix
country: United States
facility: Hope Research Institute, LLC
state: Arizona
city: Tucson
country: United States
facility: Visions Clinical Research-Tucson
state: Arizona
city: Carmichael
country: United States
facility: Northern California Research Corp
state: California
city: Colton
country: United States
facility: Arrowhead Regional Medical Center
state: California
city: Costa Mesa
country: United States
facility: Robin Black OGNP
state: California
city: San Diego
country: United States
facility: IGO Medical Group of San Diego
state: California
city: New London
country: United States
facility: Coastal Connecticut Research, LLC
state: Connecticut
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Boynton Beach
country: United States
facility: Visions Clinical Research
state: Florida
city: Pembroke Pines
country: United States
facility: Global OB/GYN Centers of Florida
state: Florida
city: Sarasota
country: United States
facility: Physician Care Clinical Research, LLC.
state: Florida
city: West Palm Beach
country: United States
facility: OB/GYN Specialists of the Palm Beaches
state: Florida
city: Atlanta
country: United States
facility: Mount Vernon Clinical Research, LLC
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Metairie
country: United States
facility: East Jefferson OB/GYN
state: Louisiana
city: Las Vegas
country: United States
facility: Office of R. Garn Mabey, MD
state: Nevada
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health
state: New York
city: New York
country: United States
facility: New York Downtown Hospital
state: New York
city: Cincinnati
country: United States
facility: Greater Cincinnati OB/GYN, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center Dept of OB/GYN
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services
state: Pennsylvania
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Austin
country: United States
facility: Hill Country OB/GYN
state: Texas
city: Houston
country: United States
facility: Planned Parenthood of Houston & Southeast Texas, Inc.
state: Texas
city: Plano
country: United States
facility: 4601 Old Shepard Place; Bldg 2, Suite 201
state: Texas
Study officials:
affiliation: OB/GYN Specialists of the Palm Beaches
name: John A Burigo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Arrowhead Regional Medical Center
name: Ramon Cestero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Planned Parenthood of Houston & Southeast Texas, Inc.
name: Paul M Fine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Visions Clinical Research
name: Keith A Aqua, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mount Vernon Clinical Research, LLC
name: Steven C Blank, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northern California Research Corp
name: Douglas G Young, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hope Research Institute, LLC
name: Allan T Sawyer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montefiore Medical Center-Weiler Division
name: Mark H Einstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Coastal Connecticut Research, LLC
name: Robert M Spitz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Greater Cincinnati OB/GYN, Inc.
name: Thomas A deHoop, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jacobi Medical Center
name: Lance R Bruck, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alabama Highlands, Dept. of OB/GYN
name: Warner K Huh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Presbyterian Hospital
name: Giuseppe Del Priore, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oklahoma Health Sciences Center Dept of OB/GYN
name: Michael A Gold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services
name: Richard S Guido, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IGO Medical Group of San Diego
name: Philip E Young, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Augusta University
name: Daron G. Ferris, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Visions Clinical Research-Tucson
name: Cynthia J Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hill Country OB/GYN
name: Ana Eduardo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OB/GYN
name: Phyllis Gee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Robin Black OGNP, Costa Mesa California
name: Robert Pfeffer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medstar Health Research Institute
name: Jonathan A Cosin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: South Carolina Oncology Associates
name: James A Williams, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: East Jefferson OB/GYN
name: Vincent A Culotta, Jr, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Physician Care Clinical Research, LLC.
name: G. Michael Swor, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Office of R. Garn Mabey, MD
name: Garn R Mabey, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lehigh Valley Hospital
name: Martin Martino, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Global OB/GYN Centers of Florida
name: Robert Klein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jersey Shore University Medical Center
name: William J Mann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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