Clinical Trials /

Ruxolitinib for Premalignant Breast Disease

NCT02928978

Description:

This study is evaluating how ruxolitinib affects premalignant breast cells. One half of the study participants will receive ruxolitinib for approximately 15 days, and the other half will receive a placebo (sugar pill) for approximately 15 days. Once study participants have completed their ruxolitinib or placebo, participants will undergo surgery to remove the premalignant breast tissue.

Related Conditions:
  • Atypical Ductal Breast Hyperplasia
  • Atypical Lobular Breast Hyperplasia
  • Breast Lobular Carcinoma In Situ
  • Ductal Carcinoma In Situ
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib for Premalignant Breast Disease
  • Official Title: TBCRC 042 - A Randomized Phase II Window-of-Opportunity Trial of Ruxolitinib in Patients With High Risk and Premalignant Breast Conditions

Clinical Trial IDs

  • ORG STUDY ID: H-38855
  • NCT ID: NCT02928978

Conditions

  • Ductal Carcinoma In Situ
  • Atypical Lobular Hyperplasia
  • Atypical Ductal Hyperplasia
  • Lobular Carcinoma In Situ

Interventions

DrugSynonymsArms
RuxolitinibJakafi, INCB018424 PhosphateRuxolitinib
Placebo (for Ruxolitinib)Placebo

Purpose

This study is evaluating how ruxolitinib affects premalignant breast cells. One half of the study participants will receive ruxolitinib for approximately 15 days, and the other half will receive a placebo (sugar pill) for approximately 15 days. Once study participants have completed their ruxolitinib or placebo, participants will undergo surgery to remove the premalignant breast tissue.

Trial Arms

NameTypeDescriptionInterventions
RuxolitinibExperimentalParticipants will receive ruxolitinib 20 mg by mouth twice daily for 15 days (+/- 5 days). Ruxolitinib will be supplied as four, 5 mg tablets.
  • Ruxolitinib
PlaceboPlacebo ComparatorParticipants will receive a placebo (sugar pill) that is designed to mimic ruxolitinib. The placebo will be supplied as four, 5 mg tablets. Participants assigned to this arm will take four, 5 mg tablets by mouth twice daily for 15 days (+/- 5 days).
  • Placebo (for Ruxolitinib)

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.

               -  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.

          -  Women and men age 18 and older.

          -  Adequate hematologic and organ function, defined as follows:

               -  Absolute neutrophil count ≥ 1500/mm3

               -  Hemoglobin ≥ 9.0 g/dL

               -  Platelet levels >200 x 109/L

               -  Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)

               -  AST/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, conivaptan,
             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.

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Apoptosis
Time Frame:15 days (+/- 5 days)
Safety Issue:
Description:The number of premalignant breast cells in apoptosis at the time of diagnosis will be compared to the number of cells in apoptosis following treatment with 15 (+/- 5) days of ruxolitinib or placebo.

Secondary Outcome Measures

Measure:pSTAT5
Time Frame:15 days (+/- 5 days)
Safety Issue:
Description:To determine the difference in change in pSTAT5 levels between diagnosis and surgery as a function of ruxolitinib treatment versus placebo

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Julie Nangia

Trial Keywords

  • Premalignant Breast Disease
  • ALH
  • ADH
  • DCIS
  • LCIS
  • Breast Cancer Prevention
  • Ruxolitinib

Last Updated

November 18, 2019