Atypical Ductal Hyperplasia, Atypical Lobular Hyperplasia, Ductal Carcinoma In Situ, Lobular Carcinoma In Situ
Conditions
Keywords
Premalignant Breast Disease, ALH, ADH, DCIS, LCIS, Breast Cancer Prevention, Ruxolitinib
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.
Interventions
DRUGRuxolitinib
tablet (taken by mouth)
DRUGPlacebo (for Ruxolitinib)
tablet (taken by mouth)
Sponsors
Julie Nangia
Incyte Corporation
Translational Breast Cancer Research Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Apoptosis | 15 days (+/- 5 days) | 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
| Measure | Time frame | Description |
|---|---|---|
| Proliferation/Apoptosis Biomarkers | 15 days (+/- 5 days) | To determine the difference in change in proliferation/apoptosis biomarker levels between diagnosis and surgery as a function of ruxolitinib treatment versus placebo. Example biomarkers include: pSTAT5, TUNEL, Ki67, BclXL, Mcl1, Bcl2, PRLR, pSTAT3, and serum prolactin. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJulie Nangia, M.D.
Baylor College of Medicine
Outcome results
None listed