Ruxolitinib in Preventing Breast Cancer in Patients with High Risk and Precancerous Breast Lesions
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.
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.
- Platelets > 200 x 10^9 /L.
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and 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, conivaptanin, grapefruit juice, 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- 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.
- Human immunodeficiency virus (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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02928978.
PRIMARY OBJECTIVE:
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 24-48 days (from start of treatment until post-surgical follow-up in clinic, typically 2-4 weeks post-operative).
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorJulie Rani Nangia
- Primary IDTBCRC-042
- Secondary IDsNCI-2019-01957, RUXO H-38855
- ClinicalTrials.gov IDNCT02928978