Imiquimod in Preventing Cervical Cancer in Women With Cervical Neoplasia

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00031759

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

128.1

Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Chemoprevention therapy is the use of certain substances to try to prevent the development of cancer. Applying topical imiquimod before abnormal cervical cells are removed may be effective in preventing cervical cancer.

PURPOSE: Randomized phase II trial to study the effectiveness of applying topical imiquimod before abnormal cervical cells are removed in preventing cervical cancer in patients who have recurrent or persistent cervical neoplasia.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer Precancerous Condition	Drug: imiquimod Procedure: Ablative or excisional therapy	Phase 2

Detailed Description

OBJECTIVES:

Compare the chemopreventive efficacy of topical imiquimod followed by local ablative or excisional therapy vs ablative/excisional therapy alone in patients with recurrent or high-grade cervical intraepithelial neoplasia.
Compare the toxicity of these regimens in these patients.
Compare the quality of life of patients treated with these regimens.
Determine the safety and tolerability of imiquimod in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease (primary vs recurrent or persistent), severity of dysplasia (grade I vs grade II vs grade III), current tobacco use (yes vs no), planned surgical procedure (excisional vs laser vs cryotherapy vs other), and time since first abnormal Pap smear, including pathology of ascus favor dysplasia (less than 1 year vs 1-3 years vs more than 3 years). Patients are randomized to one of two treatment arms.

Arm I: Patients undergo ablative or excisional therapy.
Arm II: Patients have topical imiquimod applied to the cervix for 6-10 hours twice weekly for a total of 5 doses. Within 3-4 weeks after the final application, patients undergo ablative or excisional therapy.

Quality of life is assessed at baseline, after last dose of study drug (arm II only), 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter.

Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy.

PROJECTED ACCRUAL: A total of 66-152 (33-76 per treatment arm) will be accrued for this study within 18 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

57 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Phase II Topical Immunomodulatory Therapy With Imiquimod for the Chemoprevention of Recurrent and High-Grade Cervical Intraepithelial Neoplasia (CIN)

Study Start Date :

Jun 1, 1999

Actual Primary Completion Date :

Jul 1, 2004

Actual Study Completion Date :

Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: Ablative or excisional therapy Patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy.	Procedure: Ablative or excisional therapy
Experimental: Ablative or excisional therapy + imiquimod Patients have topical imiquimod applied to the cervix for 6-10 hours twice weekly for a total of 5 doses. Within 3-4 weeks after the final application, patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, after last dose of study drug, 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy.	Drug: imiquimod Procedure: Ablative or excisional therapy

Arm

Intervention/Treatment

Other: Ablative or excisional therapy

Patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy.

Procedure: Ablative or excisional therapy

Experimental: Ablative or excisional therapy + imiquimod

Patients have topical imiquimod applied to the cervix for 6-10 hours twice weekly for a total of 5 doses. Within 3-4 weeks after the final application, patients undergo ablative or excisional therapy. Quality of life is assessed at baseline, after last dose of study drug, 3-5 days after ablation or excisional therapy, at 3 months, and then annually thereafter. Patients are followed every 3-4 months until 2 consecutive normal Pap smears or colposcopic exams, every 6 months for 2 years, and then annually until 5 years after completion of study therapy.

Drug: imiquimod

Procedure: Ablative or excisional therapy

Outcome Measures

Primary Outcome Measures

Overall survival [Up to 7.5 years]

Secondary Outcome Measures

Compare the quality of life of patients treated with these regimens [Up to 7.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed primary grade II or III cervical intraepithelial neoplasia (CIN) or persistent grade I-III CIN (dysplasia that is not new and requires treatment)
Squamous cell lesions not involving endocervix by colposcopy OR colposcopy with negative cytobrush or endocervical curettage
No untreated cervical or vaginal infection other than human papilloma virus
No desire for hysterectomy as ablative therapy

PATIENT CHARACTERISTICS:

Age:

18 and over

Life expectancy:

At least 5 years

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 3 months after study
HIV negative
No AIDS
No known hypersensitivity to imiquimod
No latex allergy

PRIOR CONCURRENT THERAPY:

Other:

No concurrent immunosuppressive therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona	United States	85259-5404
2	Mayo Clinic	Jacksonville	Florida	United States	32224
3	MBCCOP - Hawaii	Honolulu	Hawaii	United States	96813
4	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
5	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
6	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
7	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
8	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57104