Clinical trial NCT02928978: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ductal Carcinoma In Situ
Atypical Lobular Hyperplasia
Atypical Ductal Hyperplasia
Lobular Carcinoma In Situ
Keywords: Premalignant Breast Disease
ALH
ADH
DCIS
LCIS
Breast Cancer Prevention
Ruxolitinib
Lead sponsor: Baylor Breast Care Center
Sponsor class: OTHER
Collaborators: name: Incyte Corporation
name: Translational Breast Cancer Research Consortium
First posted: 2016-10-10
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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 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.
* If the patient undergoes germline genetic testing, the results must be received prior to randomization, as the results may affect the surgical approach and, in turn, the date of surgical excision.
* Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign a written informed consent document.

Exclusion Criteria:

* Treatment with selective estrogen receptor modulators (SERMs) or aromatase inhibitors for breast cancer prevention within 1 year prior to starting study treatment.
* Treatment with any other investigational agents within 30 days of starting study treatment.
* Current diagnosis of invasive breast cancer (current microinvasive disease is allowed), or previous history of invasive breast cancer diagnosed within the last 5 years.

NOTE: If previous history of ER+ invasive breast cancer diagnosed \> 5 years ago, patient must be off endocrine therapy for at least 1 year prior to starting study treatment.

* 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.
* Women who are pregnant or nursing.
* HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ruxolitinib.
* Prior or current treatment with a JAK inhibitor, for any indication.
* Known active Hepatitis B or C.

Primary outcomes:
measure: Change in Apoptosis
timeFrame: 15 days (+/- 5 days)
Secondary outcomes:
measure: pSTAT5
timeFrame: 15 days (+/- 5 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Harris Health System - Smith Clinic
state: Texas
city: Houston
country: United States
facility: O'Quinn Medical Tower - McNair Campus; Dan L Duncan Comprehensive Cancer Center
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: Julie Nangia, M.D.
role: PRINCIPAL_INVESTIGATOR
References: