Ruxolitinib for Premalignant Breast Disease (TBCRC042)

• ClinicalTrials.gov Identifier: NCT02928978
• Recruitment Status: Recruiting
• First Posted: October 10, 2016
• Last Update Posted: May 12, 2022
• Sponsor: Julie Nangia
• Collaborators: Incyte Corporation; Translational Breast Cancer Research Consortium
• Information provided by (Responsible Party): Julie Nangia, Baylor Breast Care Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Ductal Carcinoma In Situ; Atypical Lobular Hyperplasia; Atypical Ductal Hyperplasia; Lobular Carcinoma In Situ	Drug: Ruxolitinib; Drug: Placebo (for Ruxolitinib)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: TBCRC 042 - A Randomized Phase II Window-of-Opportunity Trial of Ruxolitinib in Patients With High Risk and Premalignant Breast Conditions
• Actual Study Start Date: May 13, 2018
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: January 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ruxolitinib; 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; tablet (taken by mouth); Other Names: Jakafi; INCB018424
Placebo Comparator: Placebo; 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); tablet (taken by mouth)

Outcome Measures

Primary Outcome Measures :

1. Change in Apoptosis [ Time Frame: 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 Outcome Measures :

1. pSTAT5 [ Time Frame: 15 days (+/- 5 days) ]
   To determine the difference in change in pSTAT5 levels between diagnosis and surgery as a function of ruxolitinib treatment versus placebo

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Kristen Otte; 713-798-8874; clinical-research@breastcenter.tmc.edu

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35294

Contact: Shelley Hill 205-934-4173 shill26@uab.edu

Principal Investigator: Catherine Parker, MD

United States, Indiana

Indiana University Melvin and Bren Simon Cancer Center; Recruiting

Indianapolis, Indiana, United States, 46202

Contact: Versie Barnes 317-278-3127 barnesv@iu.edu

Principal Investigator: Carla Fisher, MD

United States, New York

Montefiore Medical Center; Recruiting

Bronx, New York, United States, 10461

Contact: Anton Lulaj 718-405-8539 alulaj@montefiore.org

Principal Investigator: Sheldon Feldman, MD

United States, North Carolina

University of North Carolina at Chapel Hill; Recruiting

Chapel Hill, North Carolina, United States, 27599

Contact: Crissey Tait 984-974-8675 crissey_tait@med.unc.edu

Principal Investigator: Kristalyn Gallagher, DO

United States, Tennessee

Vanderbilt-Ingram Cancer Center; Recruiting

Nashville, Tennessee, United States, 37232

Contact: Clinical Trials Information Program 800-811-8480

Principal Investigator: Ingrid Meszoely, MD

United States, Texas

Baylor College of Medicine; Recruiting

Houston, Texas, United States, 77030

Contact: Claudette Foreman 713-798-7315 cforema@bcm.edu

Principal Investigator: Julie Nangia, M.D.

Sub-Investigator: Mothaffar Rimawi, M.D.

Sub-Investigator: Bora Lim, M.D.

Sub-Investigator: C. Kent Osborne, M.D.

University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Diane Weber, RN 346-212-1287 dweber@mdanderson.org

Principal Investigator: Parijatham Thomas, MD

Sponsors and Collaborators

Julie Nangia

Incyte Corporation

Translational Breast Cancer Research Consortium

Investigators

• Principal Investigator: Julie Nangia, M.D.; Baylor College of Medicine

More Information

• Responsible Party: Julie Nangia, Assistant Professor, Baylor Breast Care Center
• ClinicalTrials.gov Identifier: NCT02928978
• Other Study ID Numbers: H-38855
• First Posted: October 10, 2016
• Last Update Posted: May 12, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Julie Nangia, Baylor Breast Care Center:

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

Additional relevant MeSH terms:

Carcinoma; Carcinoma in Situ; Carcinoma, Ductal; Carcinoma, Intraductal, Noninfiltrating; Precancerous Conditions; Carcinoma, Lobular; Breast Carcinoma In Situ; Breast Diseases; Hyperplasia; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pathologic Processes; Adenocarcinoma; Neoplasms, Ductal, Lobular, and Medullary; Skin Diseases; Breast Neoplasms; Neoplasms by Site