Ruxolitinib in Preventing Breast Cancer in Patients with High Risk and Precancerous Breast Lesions

Status: Active

Description

This phase II trial studies how well ruxolitinib before surgery works in preventing breast cancer in patients with high risk and precancerous breast conditions. Ruxolitinib may changes the breast cell when administered to participants with precancerous breast conditions. Ruxolitinib may stop the growth of cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

Inclusion Criteria

  • Have a breast biopsy showing ADH (atypical ductal hyperplasia), ALH (atypical lobular hyperplasia), LCIS (lobular carcinoma in situ), or DCIS (ductal carcinoma in situ) requiring surgical excision. Microinvasive disease is allowed. The number of participants with DCIS will be limited to no more than 15 in each arm. * NOTE: Tissue from the diagnostic biopsy must be accessible/available for research correlates (i.e., a tissue block or ~10 unstained slides). Due to the nature of the study, fewer slides may be accepted with prior permission from the Protocol Chair if there is insufficient tissue.
  • Absolute neutrophil count >= 1500/mm^3.
  • Hemoglobin >= 9.0 g/dL.
  • Platelet levels > 200 x 10^9 /L (must be within 4 weeks of starting therapy; this cut-off was chosen because the dose of ruxolitinib must be reduced with lower platelet counts).
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN).
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x institutional ULN.
  • Alkaline phosphatase =< 5 x institutional ULN.
  • Creatinine clearance > 50 mL/min as calculated by the Cockcroft-Gault method.
  • Willing to not use concomitant strong CYP3A4 inhibitors as this could interfere with the metabolism of ruxolitinib (i.e azole antifungals, clarithromycin, conivapin, grapefruit juice, mibefradil, nefazodone, protease inhibitors, telithromycin).
  • Women of child bearing potential must have a negative pregnancy test prior to starting therapy. The effects of ruxolitinib on the developing human fetus are unknown. For this reason and because class C agents are potentially teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

  • Participants may not be receiving any other investigational agents within 30 days of enrollment.
  • Participants with current or previous history of invasive breast cancer (current microinvasive disease is allowed).
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, end stage renal disease (ESRD), or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or nursing women are excluded from this study.
  • Human immunodeficiency virus (HIV) positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ruxolitinib. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Prior or current treatment with a JAK inhibitor, for any indication.
  • Known hepatitis B or C participants.

Locations & Contacts

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: Approved
Contact: Stephanie Downs-Canner
Phone: 919-966-4416
Email: stephanie_downs-canner@med.unc.edu

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Contact: Ingrid Marie Meszoely
Email: ingrid.meszoely@vumc.org

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: Active
Contact: Julie Rani Nangia
Phone: 713-798-1311
Email: nangia@bcm.edu
Ben Taub General Hospital
Status: Active
Contact: Julie Rani Nangia
Phone: 713-798-1311
Email: nangia@bcm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the difference in change in apoptosis between diagnosis and surgery as a function of ruxolitinib treatment versus placebo, among participants with high-risk or premalignant breast conditions.

SECONDARY OBJECTIVES:

I. To determine the difference in change in phosphorylated (p)STAT5 levels between diagnosis and surgery as a function of ruxolitinib treatment versus placebo.

II. To determine if pre and post-treatment pSTAT5 levels are inversely correlated with baseline apoptosis.

III. In patients treated with ruxoloitinib, to determine the difference in change in apoptosis between diagnosis and surgery as a function of lesion size (i.e. ductal carcinoma in situ [DCIS] > 2 cm compared to others).

IV. To perform an exploratory analysis of other biomarkers (TdT-mediated dUTP nick end labeling assay [TUNEL], Ki67, BclXL, Mcl1, Bcl2, PRLR, pSTAT3, and serum prolactin levels).

V. To determine if, at baseline and at surgery, differences in menstrual cycle are associated with differences in pSTAT5.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Beginning at least 10 days prior to planned surgical excision of premalignant breast lesion, patients receive ruxolitinib orally (PO) twice daily (BID) for 15 days (+/- 5 days, with dosing not to exceed 20 days) in the absence of disease progression or unacceptable toxicity. Within 12 hours of the last dose, patients undergo standard of care surgery.

ARM II: Beginning at least 10 days prior to planned surgical excision of premalignant breast lesion, patients receive placebo PO BID for 15 days (+/- 5 days, with dosing not to exceed 20 days) in the absence of disease progression or unacceptable toxicity. Within 12 hours of the last dose, patients undergo standard of care surgery.

After completion of study treatment, patients are followed up for 28-48 days (from start of treatment until post-surgical follow-up in clinic, typically 2-4 weeks post-operative).

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Julie Rani Nangia

Trial IDs

Primary ID TBCRC-042
Secondary IDs NCI-2019-01957, RUXO H-38855
Clinicaltrials.gov ID NCT02928978