Ruxolitinib for Precancerous Breast Conditions

(TBCRC042 Trial)

Not currently recruiting at 9 trial locations

Overseen By Kristen Otte

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Julie Nangia

Must not be taking: SERMs, Aromatase inhibitors, JAK inhibitors, others

Disqualifiers: Invasive breast cancer, ESRD, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 15 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how ruxolitinib, a medication, affects precancerous breast conditions such as atypical ductal hyperplasia or lobular carcinoma in situ. Participants will receive either ruxolitinib or a placebo for about 15 days before surgery to remove the affected breast tissue. The trial targets individuals diagnosed with these specific breast conditions who are scheduled for surgery. Researchers aim to determine if ruxolitinib can treat these premalignant cells. Participants should not have recently received certain breast cancer medications or have an active invasive breast cancer diagnosis. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

Will I have to stop taking my current medications?

The trial requires that you do not use strong CYP3A4 inhibitors (like certain antifungals and grapefruit juice) while participating, as they can interfere with the study drug. If you are taking selective estrogen receptor modulators or aromatase inhibitors, you must have stopped them at least a year before starting the study.

Is there any evidence suggesting that ruxolitinib is likely to be safe for humans?

Research has shown that ruxolitinib, a treatment under study, has been tested for conditions like graft-versus-host disease and metastatic breast cancer. These studies indicate that while ruxolitinib can be effective, it also carries some risks.

Some individuals taking ruxolitinib have experienced side effects such as infections and an increased likelihood of serious issues, including heart problems, cancer, and blood clots. There is also a heightened risk of death from various causes. However, the FDA has approved ruxolitinib for other uses, indicating that its safety is considered acceptable when the benefits outweigh the risks.

These findings provide insight into its safety, but it is crucial for anyone considering joining a trial to discuss these risks with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ruxolitinib is unique because it targets the JAK-STAT signaling pathway, which is different from most standard treatments for precancerous breast conditions, like surgery or hormone therapies. This pathway plays a crucial role in cell growth and immune function, so by inhibiting it, ruxolitinib may help reduce abnormal cell growth and inflammation more directly. Researchers are excited about this treatment because it offers the potential for a non-surgical option that works at the molecular level, potentially offering quicker and more targeted results.

What evidence suggests that ruxolitinib might be an effective treatment for precancerous breast conditions?

Research has shown that ruxolitinib can lower the activity of certain proteins that help breast cancer cells grow, particularly a protein called STAT3. Early lab studies using breast cancer cells have demonstrated this effect. Initial studies also suggest that ruxolitinib, a drug that blocks certain enzymes involved in cell growth, might help treat some aggressive types of breast cancer. Evidence indicates that ruxolitinib can kill cancer cells when used before surgery in cases of inflammatory breast cancer. In this trial, participants will receive either ruxolitinib or a placebo to evaluate its effectiveness in treating early-stage breast conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Julie Nangia, M.D.

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with certain non-invasive breast conditions like ADH, ALH, LCIS, or DCIS needing surgery. Participants must not be pregnant/nursing, HIV-positive on antiretrovirals, have had JAK inhibitors before, active hepatitis B/C, recent SERMs/aromatase inhibitors use for prevention or invasive breast cancer history within 5 years.

Inclusion Criteria

Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign a written informed consent document.

My biopsy samples are available for research.

My blood and organs are functioning well.

Exclusion Criteria

I have taken medication to prevent breast cancer in the last year.

I do not have any severe illnesses that could interfere with the study.

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ruxolitinib or placebo for approximately 15 days

15 days

Surgery

Participants undergo surgery to remove the premalignant breast tissue

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib
• Surgery

Trial Overview The study tests if ruxolitinib affects premalignant breast cells compared to a placebo. Half the participants will take ruxolitinib and half a sugar pill for about 15 days before surgical removal of the affected tissue.

How Is the Trial Designed?

Group I: Ruxolitinib Experimental Treatment 1 Intervention

Participants will receive ruxolitinib 20 mg by mouth twice daily for 15 days (+/- 5 days). Ruxolitinib will be supplied as four, 5 mg tablets.

Group II: Placebo Placebo Group 1 Intervention

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).

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Julie Nangia

Lead Sponsor

Trials

2

Recruited

340+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

In a phase II study of 23 patients with refractory metastatic triple-negative breast cancer, ruxolitinib was well-tolerated with minimal severe side effects, primarily causing fatigue.

Despite showing on-target activity by reducing pSTAT3+ cells in some patients, ruxolitinib did not achieve any objective responses, indicating it may not be effective as a single-agent treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer. Stover, DG., Gil Del Alcazar, CR., Brock, J., et al.[2020]

Ruxolitinib, a JAK-2 inhibitor used for treating myeloproliferative neoplasms, is generally associated with very rare skin toxicity, but an unusual case of erythematous skin eruption with necrotic centers was observed in a patient with primary myelofibrosis.

This case highlights the need for increased awareness of potential skin side effects from ruxolitinib, especially as JAK-2 inhibitors may be used more widely in dermatological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. Dasanu, CA.[2021]

The combination of Ruxolitinib and Exemestane was found to be safe for patients with hormone-receptor positive metastatic breast cancer, although a dose reduction was necessary due to anemia in some patients.

Despite its safety, the treatment showed minimal clinical activity, with only a 24% clinical benefit rate and a median progression-free survival of 2.8 months, indicating a need for more effective therapies targeting inflammation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer. Makhlin, I., McAndrew, NP., Wileyto, EP., et al.[2023]

A study analyzing 126,815 safety reports found that the JAK inhibitors ruxolitinib, tofacitinib, and baricitinib are associated with increased risks of infectious adverse events, particularly viral, fungal, and mycobacterial infections.

Tofacitinib specifically showed a significant association with gastrointestinal perforation events, while no significant increase in major cardiovascular events was observed, indicating a need for careful monitoring of these risks in patients using JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Hoisnard, L., Lebrun-Vignes, B., Maury, S., et al.[2023]

The combination of antiestrogen therapy and ribociclib, a CDK4/6 inhibitor, significantly improved progression-free survival in women with metastatic HR-positive, HER2-negative breast cancer compared to letrozole alone.

These findings come from a large phase III trial, which may support FDA approval for this combination treatment, highlighting its potential efficacy in managing this type of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ribociclib Lengthens Breast Cancer Survival. [2018]

Ruxolitinib, a Janus kinase inhibitor approved for myelofibrosis and polycythemia vera, shows promising efficacy in treating dermatologic conditions like atopic dermatitis, psoriasis, and vitiligo, based on data from clinical trials.

The evidence for ruxolitinib's effectiveness in alopecia areata is mixed, varying between topical and oral formulations, indicating the need for further research to clarify its role in treating various skin disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. Tegtmeyer, K., Ravi, M., Zhao, J., et al.[2021]

Ruxolitinib, a JAK1 and JAK2 inhibitor used for myelofibrosis and polycythemia vera, showed no carcinogenic potential in long-term studies with Tg.rasH2 mice and Sprague-Dawley rats, indicating it does not increase cancer risk.

Despite some pharmacological effects like lymphoid depletion and inflammation, ruxolitinib did not affect survival rates or increase neoplastic findings, suggesting it is safe for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. Shuey, DL., Oliver, J., Zhou, G., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8487317/

Phase I/II Trial of Ruxolitinib in Combination with ... Pre-clinical data have demonstrated that treatment of HER2+ breast cancer cell models with ruxolitinib decreases STAT3 phosphorylation, decreases tumor ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01562873

NCT01562873 | Ruxolitinib in Patients With Breast Cancer This study is testing the effects of ruxolitinib in patients with breast cancer.

3. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-024-01774-0

TBCRC 039: a phase II study of preoperative ruxolitinib with or ... Preclinical studies implied that ruxolitinib (RUX), a JAK1/2 inhibitor, may be an effective therapy for TN-IBC.

4. clinicaltrial.be clinicaltrial.be/fr/details/9894?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=100

Study Of Ruxolitinib (INCB018424) With Preoperative ... They have been shown to result in death of cancer cells when given as preoperative treatment of women with inflammatory breast cancer (IBC).

5. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-results-phase-3-clinical-trials-evaluating

Incyte Announces Results of Phase 3 Clinical Trials ... As a result, significantly more patients who applied ruxolitinib cream 1.5% versus vehicle control achieved overall treatment success (11.9% vs ...

6. hcp.jakafi.com hcp.jakafi.com/acute-graft-versus-host-disease/safety-adverse-events

Safety Profile of Jakafi in aGVHD Safety results for Jakafi ® (ruxolitinib) in REACH1 · Nonhematologic Adverse Reactions Occurring in ≥15% of Patients · Selected Laboratory Abnormalities Worsening ...

7. opzelura.com opzelura.com/opzelura-prescribing-information

Prescribing Information Serious Infections: OPZELURA contains ruxolitinib. · Increased risk of death due to any reason (all causes): · Cancer and immune system problems: · Increased risk ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2025/215309s007lbl.pdf

OPZELURA® (ruxolitinib) cream, for topical use The safety and effectiveness of OPZELURA have not been established in pediatric patients younger than 12 years of age with nonsegmental vitiligo. Juvenile ...

9. incytemi.com incytemi.com/document/Poster/Fall%20Clinical%202025_Bunick%20CG_Rux%20Cream%20Integrated%20Safety%20Analysis.pdf

Integrated Safety Analysis of Ruxolitinib Cream FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5935675/

Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in ... We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer. This was a non-randomized phase II study ...