Ruxolitinib for Precancerous Breast Conditions

(TBCRC042 Trial)

Recruiting at 8 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

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if ruxolitinib can change early abnormal breast cells that might turn into cancer. Some participants will take the drug for a short period, while others will not. Afterward, all participants will have surgery to remove the abnormal cells. Ruxolitinib has been evaluated in various clinical trials for treating certain types of breast cancer.

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.

What data supports the effectiveness of the drug Ruxolitinib for precancerous breast conditions?

Research on Ruxolitinib combined with exemestane in advanced breast cancer showed it was safe but had limited effectiveness, with a 24% clinical benefit rate and modest impact on disease progression. This suggests Ruxolitinib may have some potential in breast cancer treatment, but more effective therapies are needed. ^{1 2 3 4 5}

Is Ruxolitinib generally safe for humans?

Ruxolitinib has been associated with an increased risk of skin cancers and infectious diseases in some patients. However, studies in animals did not show an increase in cancer risk, and some adverse effects like skin reactions are rare. ^{6 7 8 9 10}

How is the drug Ruxolitinib unique for treating precancerous breast conditions?

Ruxolitinib is unique because it targets the JAK1 and JAK2 proteins, which are part of a signaling pathway involved in cell growth and survival, and this pathway is often active in certain types of breast cancer. Unlike other treatments, it is taken orally and has been shown to affect the JAK-STAT pathway, which is important in breast cancer cell regulation. ^{6 9 11 12 13}

Research Team

Julie Nangia, M.D.

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Ribociclib Lengthens Breast Cancer Survival. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Intrinsic subtype and overall survival of patients with advanced HR+/HER2- breast cancer treated with ribociclib and ET: correlative analysis of MONALEESA-2, -3, -7. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Chemotherapy response and survival of inflammatory breast cancer by hormone receptor- and HER2-defined molecular subtypes approximation: an analysis from the National Cancer Database. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Off-label Studies on the Use of Ruxolitinib in Dermatology. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Aggressive Skin Cancers Occurring in Patients Treated With the Janus Kinase Inhibitor Ruxolitinib. [2021]

8. England pubmed.ncbi.nlm.nih.gov

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

9. Netherlands pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Phase I/II trial of ruxolitinib in combination with trastuzumab in metastatic HER2 positive breast cancer. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Phase I study of JAK1/2 inhibitor ruxolitinib with weekly paclitaxel for the treatment of HER2-negative metastatic breast cancer. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer. [2020]