A Prevention Trial in Subjects at High Risk for Breast Cancer

NCT01500577 | Completed Phase 2

• 2 other identifiers: IEO S222/6042004-005267-21
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the proposed trial is to assess. The efficacy and the safety of a daily administration of nimesulide or simvastatin to change the expression of a large set of tissue and circulating surrogate endpoint biomarkers (SEBs) of breast carcinogenesis in women at higher risk of developing a hormone non-responsive (ER neg) breast cancer. The primary endpoint is the change in prevalence of atypical cells and cellular proliferation (Ki-67), after 12 months of treatment.

Conditions

Breast Cancer

Keywords

Prevention; Breast Cancer; Proliferation; Breast Cancer Prevention

Outcome Measures

Primary Outcomes (1)

• Ki 67 variation

  changes of cellular proliferation marker Ki-67 in blood, ductal lavage fluid at the end of treatment withe respect to baseline. A further assessment will be done at the end of a furter 12 months follow-up.

  baseline and 12 months

Secondary Outcomes (1)

• plasma IGF-I, IGFBP-1-2-3, estradiol, estrone sulphate, DHEA-sulphate, SHBG, C-reactive protein, prolactin

  2 years

Study Arms (3)

Nimesulide

EXPERIMENTAL

Nimesulide 100 mg (capsules), 100mg/die every day for 1 year. Oral administration

Drug: nimesulide

Simvastatin

EXPERIMENTAL

Simvastatin 20 mg (capsules). 20mg/die every day for 1 year. Oral administration

Drug: Simvastatin

Placebo

PLACEBO COMPARATOR

Placebo (capsules). 1 cps/die every day for 1 year. Oral administration

Other: Placebo

Interventions

nimesulide DRUG

Nimesulide 100 mg (capsules). 100mg/die every day for 1 year. Oral administration

Also known as: Aulin

Nimesulide

Simvastatin DRUG

Simvastatin 20 mg (capsules). 20mg/die every day for 1 year. Oral administration

Also known as: Sivastin

Simvastatin

Placebo OTHER

Placebo (capsules). 1 cps/die every day for 1 year. Oral administration

Placebo

Eligibility Criteria

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

You may qualify if:

• Female, 18-65 years old inclusive
• Histologic confirmation of hormone non-responsive DCIS (ER\<5%, PgR\<5%), or AH or LIN, radically excised in the previous 12 months;
• Positivity for BRCA1 mutation;
• \>10% probability of being a BRCA1/2 mutation carrier, according to Berry Parmigiani and/or Couch model;
• Performance Status (SWOG) = 0;
• Unwillingness to be pregnant during the study and three months after drug suspension. Women will be informed that the use of contraceptive pill is contraindicated because it may interfere with the study drugs and may be harmful to a woman who has been diagnosed with breast cancer;
• Willingness to sign the informed consent form

You may not qualify if:

• Evidence of residual disease as documented by mammograms, histologic confirmation of margin involvement or distant disease;
• Previous or concurrent malignancy (with the exception of basal cell carcinoma and CIN);
• Severe gastrointestinal disorders;
• Current use of NSAIDs;
• Current use of statins
• Current use of fibrates
• Current use of potent CYP3A4 inhibitors (ciclosporin, mibefradil, itraconazole, ketoconazole, erythromycin, clarithromycin)
• Proven hypersensitivity to nimesulide and/or simvastatin;
• Mild or higher alterations of hematologic, liver and renal function (i.e., WBC \<3,500/mm3, Plt \<120,000/mm3, HgB \<10 g/dL, AST \>45 U/L, ALT \>45 U/L, creatinin \>1.5 mg/dL, bilirubin \>1.15 mg/dL, CPK 250 mg/dL);
• CNS diseases and major psychiatric diseases or inability to comply to the protocol procedures;
• Active infections;
• Cardiac failure, class I-IV ;
• Current anticoagulant or antiplatelet aggregation therapy;
• Mitral and/or tricuspid valvulopathy or valvular prosthesis; Angina; Severe arterial hypertension; Chronic and/or paroxysmal atrial fibrillation; Previous myocardial infarction;
• Current childbearing and inability to prevent it during the intervention period and for at least 3 months after cessation of treatment;

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

European Institute of Oncology

Milan, Italy

Location

Related Publications (1)

• Lazzeroni M, Guerrieri-Gonzaga A, Serrano D, Cazzaniga M, Mora S, Casadio C, Jemos C, Pizzamiglio M, Cortesi L, Radice D, Bonanni B. Breast ductal lavage for biomarker assessment in high risk women: rationale, design and methodology of a randomized phase II clinical trial with nimesulide, simvastatin and placebo. BMC Cancer. 2012 Dec 5;12:575. doi: 10.1186/1471-2407-12-575.

  PMID: 23216985 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

nimesulide; Simvastatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2011
• First Posted: December 28, 2011
• Study Start: April 1, 2005
• Primary Completion: November 1, 2012
• Study Completion: July 1, 2013
• Last Updated: June 18, 2014

Record last verified: 2014-06

Locations

IT (1)