Clinical trial NCT00462813: Diindolylmethane in Treating Patients With Abnormal Cervical Cells
Official title: An Investigation Into the Effects of Diidolylmethane (BioResponse DIM®) Supplementation in Women With Low-Grade Cervical Cytological Abnormalities [CRISP-1]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Cancer
Precancerous Condition
Keywords: cervical cancer
cervical intraepithelial neoplasia grade 2
cervical intraepithelial neoplasia grade 3
cervical intraepithelial neoplasia grade 1
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-04-19
Enrollment: 3000
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

Brief summary: RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of diindolylmethane, a substance found in cruciferous vegetables, may keep cervical intraepithelial neoplasia or cervical cancer from forming.

PURPOSE: This randomized phase III trial is studying diindolylmethane to see how well it works compared to a placebo in treating patients with abnormal cervical cells.

Detailed description: OBJECTIVES:

* Compare the effect of diindolylmethane vs placebo in reducing the prevalence of histologically proven high-grade cervical intraepithelial neoplasia in patients with low-grade cervical cytological abnormalities.
* Compare the effect of these regimens in reducing the prevalence of cytological abnormalities in these patients.
* Compare the effect of these regimens in changing the clinical appearance of the cervix in these patients.
* Determine if diindolylmethane offers benefits in relation to human papillomavirus (HPV) status, including HPV type, viral load, and integration.
* Determine the side effects of supplementation with diindolylmethane.
* Determine the effects of this drug on migraine, mastalgia, weight, and premenstrual syndrome (PMS).

OUTLINE: This is a double-blind, randomized, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive oral diindolylmethane once daily for 6 months.
* Arm II: Patients receive oral placebo once daily for 6 months. Patients undergo cervical sampling at baseline and at 6 months for Pap testing by liquid based cytology and human papillomavirus (HPV) testing by polymerase chain reaction. Some patients also undergo urine and hair sample collection at baseline and at 3 and 6 months. Samples are analyzed for estrogen and diindolylmethane metabolites, to monitor patient compliance and response to treatment. Some patients have a cervical photograph taken using a colposcope at baseline and at 6 months. All patients undergo colposcopy at 6 months.

Patients complete a questionnaire at baseline (i.e., for reproductive history, diet, smoking, and premenstrual symptoms) and at 6 months (i.e., for side effects, compliance, changes in smoking, and contraception use). Patients with moderate to severe premenstrual syndrome (PMS) also complete PMS questionnaires once monthly during months 1-6 and 4 months following completion of study therapy. All patients are instructed to maintain current diet and to keep cruciferous vegetables and soy products constant during study course.

After completion of study treatment, patients are followed periodically for up to 7 years.

PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* First mildly dyskaryotic Pap smear or a second borderline Pap smear taken within the Cervical Screening Wales program

  * Patients under surveillance following treatment for high-grade cervical intraepithelial neoplasia are not eligible
* No clinical suspicion of a concurrent invasive cervical cancer

PATIENT CHARACTERISTICS:

* No invasive cancer within the past 3 years
* No known HIV positivity
* Not pregnant or nursing
* Not planning to become pregnant within the next 6 months

PRIOR CONCURRENT THERAPY:

* No concurrent immunosuppressive drugs, warfarin, or theophylline
* No concurrent proton pump inhibitor drugs for ulcer or reflux disease (i.e., rabeprazole, esomeprazole magnesium, lansoprazole, omeprazole, or pantoprazole sodium)

Primary outcomes:
measure: Biopsy confirmed high-grade cervical intraepithelial neoplasia (CIN) at 6 months
Secondary outcomes:
measure: Change in lesion size at 6 months
measure: Human papillomavirus (HPV) status and characteristics (type, viral load, and integration) at baseline and 6 months
measure: Change in cervical cytology at 6 months
measure: CIN ≥ grade 3 on histology at 6 months
measure: Long term follow-up (i.e., 7 years)
measure: Migraine, premenstrual syndrome (PMS), menstruation, and body weight
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Barts and the London School of Medicine
state: England
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: Barts and the London School of Medicine and Dentistry
name: Peter Sasieni, MD
role: STUDY_CHAIR
References: