Study Of Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer

NCT ID: NCT02876302

Last Updated: 2026-02-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-24
• Study Completion Date: 2026-04-30

Brief Summary

This research study is studying Ruxolitinib as possible treatment for Inflammatory Breast Cancer (IBC).

The Following drugs will be use in combination with Ruxolinitinib.

• Paclitaxel (also called Taxol)
• Doxorubicin also called Adriamycin
• Cyclophosphamide, also called Cytoxan

Detailed Description

This is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (U.S. Food and Drug Administration) has not approved Ruxolitinib for Inflammatory Breast Cancer (IBC), but is has been approved for other uses.

Ruxolitinib is a newly discovered drug that has been shown to block a pathway (called the IL6/JAK/Stat pathway) that may be important in cancer, including triple negative inflammatory breast cancer. Ruxolitinib brings proteins groups together, which can result in gene (DNA) changes. These DNA changes may stop cancer cells from growing.

Paclitaxel (also called Taxol), Doxorubicin and Cyclophosphamide (also called Adriamycin and Cytoxan, ("AC")) are drugs FDA approved for breast cancer patients. They have been shown to result in death of cancer cells when given as preoperative treatment of women with inflammatory breast cancer (IBC). Laboratory studies have shown that Ruxolitinib may make Paclitaxel more effective.

In this research study, the investigators are evaluating Ruxolitinib in combination with Paclitaxel followed by the standard chemotherapy, AC. Researchers will also evaluate how the IL6/JAK/Stat pathway is affected by this combination of drugs by studying biopsies and surgical specimens.

Conditions

Inflammatory Breast Cancer (IBC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Paclitaxel (12weeks)

Paclitaxel is administered weekly followed by standard Doxorubicin and Dyclophosphamide (AC) given every 2 weeks for 4 cycles preoperatively

• 16 patients will be randomized from the Run-In 7 days of Ruxolitinib
• The drug will be administered at a pre-determine dosage

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

15 or 20 mg, twice daily by mouth. The run-in part of ruxolitinib lasts 7 days; The treatment of ruxolitinib part lasts 12 weeks.

Paclitaxel

Intervention Type: DRUG

80 mg/m2, IV (in the vein) weekly for 12 weeks.

Doxorubicin

Intervention Type: DRUG

60 mg/m2, IV (in the vein) every 14 days for 4 doses.

Cyclophosphamide

Intervention Type: DRUG

600 mg/m2, IV (in the vein) every 14 days for 4 doses.

Ruxolitinib with Paclitaxel (12weeks)

Paclitaxel is administered with daily Ruxolitinib, followed by standard Doxorubicin and Cyclophosphamide (AC) given every 2 weeks for 4 cycles preoperatively

• 16 patients will be randomized from the Run-In 7 days of Ruxolitinib
• The drug will be administered at a pre-determine dosage

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

15 or 20 mg, twice daily by mouth. The run-in part of ruxolitinib lasts 7 days; The treatment of ruxolitinib part lasts 12 weeks.

Paclitaxel

Intervention Type: DRUG

80 mg/m2, IV (in the vein) weekly for 12 weeks.

Doxorubicin

Intervention Type: DRUG

60 mg/m2, IV (in the vein) every 14 days for 4 doses.

Cyclophosphamide

Intervention Type: DRUG

600 mg/m2, IV (in the vein) every 14 days for 4 doses.

Ruxolitinib and Paclitaxel (12weeks)

Paclitaxel is administered with daily Ruxolitinib, followed by standard Doxorubicin and Cyclophosphamide (AC) given every 2 weeks for 4 cycles preoperatively

• 32 patients will be randomized from the Run-In 7 days of Ruxolitinib + Paclitaxel
• The drug will be administered at a pre-determine dosage

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

15 or 20 mg, twice daily by mouth. The run-in part of ruxolitinib lasts 7 days; The treatment of ruxolitinib part lasts 12 weeks.

Paclitaxel

Intervention Type: DRUG

80 mg/m2, IV (in the vein) weekly for 12 weeks.

Doxorubicin

Intervention Type: DRUG

60 mg/m2, IV (in the vein) every 14 days for 4 doses.

Cyclophosphamide

Intervention Type: DRUG

600 mg/m2, IV (in the vein) every 14 days for 4 doses.

Interventions

Ruxolitinib

15 or 20 mg, twice daily by mouth. The run-in part of ruxolitinib lasts 7 days; The treatment of ruxolitinib part lasts 12 weeks.

Intervention Type: DRUG

Paclitaxel

80 mg/m2, IV (in the vein) weekly for 12 weeks.

Intervention Type: DRUG

Doxorubicin

60 mg/m2, IV (in the vein) every 14 days for 4 doses.

Intervention Type: DRUG

Cyclophosphamide

600 mg/m2, IV (in the vein) every 14 days for 4 doses.

Intervention Type: DRUG

Other Intervention Names

Jakafi; Taxol; Adriamycin; Cytoxan

Eligibility Criteria

Inclusion Criteria

• Participants must have histologically confirmed invasive breast cancer. All histologic subtypes are eligible.
• Patients must have known ER, PR, and HER2 status defined as triple-negative breast cancer (TNBC), defined as:

--ER and PR <10% by immunohistochemistry, and HER2-negative ( as per ASCO/CAP guidelines, defined as IHC 0 or 1+, or FISH ratio <2.0 or HER2 copy number <6.0).

• Patients must have the clinical diagnosis of inflammatory breast cancer, involving an intact breast.
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ruxolitinib in participants <18 years of age, children are excluded from this study.
• ECOG performance status 0 or 1.
• Participants must have normal organ and marrow function as defined below:

• Leukocytes ≥ 3,000/mm3
• Absolute neutrophil count ≥ 1,500/mm3
• Platelets ≥ 100,000/mm3
• Bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal
• Creatinine ≤1.5 x institutional upper limit of normal OR creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
• Patients with evidence of extensive nodal involvement are allowed. Extensive nodal involvement is defined as metastatic disease involving any nodal region outside of the involved breast.
• Patients with minimal metastatic disease involvement in bone or viscera are allowed. Minimal metastatic disease is defined as: evidence of metastatic involvement as demonstrated by imaging only, not amenable to biopsy confirmation.
• Both men and women are allowed.
• The effects of ruxolitinib on the developing human fetus are unknown. For this reason 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 until completion of chemotherapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.
• LVEF > 50% calculated by echocardiogram (ECHO) or MUGA
• Patients may have bilateral breast cancer so long as one breast meets criteria for inflammatory breast cancer, and neither breast cancer has received prior therapy

Exclusion Criteria

• Participants may not be receiving any other investigational agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib.
• Participants receiving any medications or substances that are potent inhibitors of CYP3A4, including grapefruit juice are ineligible. Participants receiving fluconazole are also ineligible. (Please refer to Appendix B for the full list of potent inhibitors and washout periods).
• Chronic corticosteroid use in excess of the equivalent of prednisone 10 mg once daily.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because paclitaxel, doxorubicin, and cyclophosphamide have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
• Known HIV-positive individuals on combination antiretroviral therapy are eligible so long as they meet all other criteria. Known HIV-positive individuals who are not on combination antiretroviral therapy are not eligible because these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
• Clinically significant malabsorption syndrome.
• Patients may not have received paclitaxel, doxorubicin, or cyclophosphamide as anti-neoplastic therapy.
• Patients with prior radiation to the affected breast.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Filipa Lynce, MD

Prinicipal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filipa Lynce, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University Medical Center

Durham, North Carolina, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Lynce F, Stevens LE, Li Z, Brock JE, Gulvady A, Huang Y, Nakhlis F, Patel A, Force JM, Haddad TC, Ueno N, Stearns V, Wolff AC, Clark AS, Bellon JR, Richardson ET, Balko JM, Krop IE, Winer EP, Lange P, Hwang ES, King TA, Tolaney SM, Thompson A, Gupta GP, Mittendorf EA, Regan MM, Overmoyer B, Polyak K. TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer. Breast Cancer Res. 2024 Jan 31;26(1):20. doi: 10.1186/s13058-024-01774-0.

Reference Type: DERIVED

PMID: 38297352 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16-151

Identifier Type: -

Identifier Source: org_study_id