A Two-Stage Phase 2 Study Of A-007 Topical Gel in High-Grade Squamous Intraepithelial Lesions (HSIL)

NCT00596258 | Completed Phase 2

• 1 other identifier: TG-003
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

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)

• Determine overall pathological response (complete and partial, based on independent review at month 4) of A-007 when applied topically for two 28-day cycles of 14 consec. days of treatment each to the uterine cervix of women with HSIL [CIN 2/3].

  Over the course of the trial

Secondary Outcomes (2)

• Determine the local tolerability and systemic safety of A-007.

  over the course of the trial

• Evaluate the effects of A-007 gel treatment on human papillomavirus (HPV) eradication.

  over the course of the trial

Study Arms (1)

A-007

EXPERIMENTAL

Single arm open label

Drug: A-007

Interventions

A-007 DRUG

applied topically for two 28-day cycles of 14 consecutive days of treatment each to the uterine cervix

A-007

Eligibility Criteria

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

You may qualify if:

• 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 histologic proof of CIN 2/3 disease documented within the last 12 weeks. If patient is enrolled using prior local biopsy, local slides and pathology report must be sent to the central laboratory. Patient may be enrolled into the study based on local laboratory results of CIN 2/3 and will not be discontinued if central laboratory results differ.
• Cervical swabs must test positive for high risk HPV (by Hybrid Capture 2). If the patient tests negative for high risk HPV and has proof of CIN 2/3, the patient should be retested one additional time for high-risk HPV.
• Patients must have a Hgb ≥ 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 study (until performance of the LEEP at month 4): oral, implantable, injectable contraceptives; abstinence (celibacy). Contraceptive sponges, IUD, vaginal contraceptive rings, spermacides, sponges, condoms, or partner's vasectomy are not acceptable methods of birth control.

You may not qualify if:

• Patients with CIN 1 or with invasive squamous cell carcinoma (SCC).
• CIN appearing to involve the endocervix, as assessed colposcopically
• CIN 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 who have had a LEEP performed in the past 12 months
• Patients with other malignancy (except non-melanoma skin) within the past 5 years.
• Patients with any chronic, 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 \>5 mg/d of prednisone (or its equivalent).
• Participation in another investigational medication trial concurrently or within 30 days, or prior administration of a prophylactic HPV vaccine or 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.

Sponsors & Collaborators

• Tigris Pharmaceuticals: lead

Study Sites (5)

Visions Clinical Research-Tucson

Tucson, Arizona, 85712, United States

Location

Robin Black OGNP

Costa Mesa, California, 92629, United States

Location

Visions Clinical Research

Boynton Beach, Florida, 33437, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

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

The Bronx, New York, 10461, 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

Study Officials

• Keith A Aqua, MD

  Visions Clinical Research

  PRINCIPAL INVESTIGATOR

• Mark H Einstein, MD

  Montefiore Medical Center-Weiler Division

  PRINCIPAL INVESTIGATOR

• Cynthia J Goldberg, MD

  Visions Clinical Research-Tucson

  PRINCIPAL INVESTIGATOR

• Robert Pfeffer, MD

  Robin Black OGNP, Costa Mesa California

  PRINCIPAL INVESTIGATOR

• Stephanie Blank, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 4, 2008
• First Posted: January 16, 2008
• Study Start: November 1, 2007
• Primary Completion: July 1, 2008
• Study Completion: August 1, 2008
• Last Updated: May 22, 2009

Record last verified: 2009-05

Locations

US (5)