Ruxolitinib for Premalignant Breast Disease

Study Overview
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Brief Summary
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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.

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

Conditions
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Ductal Carcinoma In Situ, Atypical Lobular Hyperplasia, Atypical Ductal Hyperplasia, Lobular Carcinoma In Situ

Intervention / Treatment
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* Drug: Ruxolitinib
* Drug: Placebo (for Ruxolitinib)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>Participants will receive ruxolitinib 20 mg by mouth twice daily for 15 days (+/- 5 days). Ruxolitinib will be supplied as four, 5 mg tablets. | Drug: Ruxolitinib<br>* tablet (taken by mouth)<br>* Other names: INCB018424;|
| Placebo Comparator: Placebo<br>Participants 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). | Drug: Placebo (for Ruxolitinib)<br>* tablet (taken by mouth)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Apoptosis | 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. | 15 days (+/- 5 days) | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALH, Premalignant Breast Disease, ADH, DCIS, LCIS, Breast Cancer Prevention, Ruxolitinib