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

NCT02876302 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-151
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 4

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

Conditions

Inflammatory Breast Cancer (IBC)

Keywords

Inflammatory Breast Cancer; Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel

  Biologic response to 7-day run-in phase treatment, defined as a change in phosphorylated STAT3 (pSTAT3) expression from moderate/high positive (pSTAT3-positive) in pre-run-in phase sample to negative or weakly positive/equivocal (pSTAT3-negative) in post-run-in samples. pSTAT3 status was determined by evaluating the percent positive cells and the strength of staining (weak vs. strong/moderate) in relation to positive and negative controls. A T-score was calculated based on percent-stained cells and intensity of staining and interpreted as follows: Scores 0-4 are negative/weakly positive (pStat3 negative) and 5-8 are moderate/high positive (pStat3 positive). Hence, pStat3 negative indicates a biologic response or a decrease in pSTAT3 levels.

  7 days

Secondary Outcomes (8)

• Pathologic Complete Response Rate (pCR) After Preoperative Therapy

  28 weeks

• Assess Change in STAT3 Gene Expression Following run-in Treatment

  7 Days

• Determine Efficacy Defined as Disease-Free Survival (DFS)

  2 years

• Determine Efficacy Defined as Time to Treatment Failure (TTF)

  2 years

• Determine Efficacy Defined as Overall Survival (OS)

  2 years

Study Arms (3)

Paclitaxel (12weeks)

EXPERIMENTAL

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

Drug: Ruxolitinib; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide

Ruxolitinib with Paclitaxel (12weeks)

EXPERIMENTAL

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

Drug: Ruxolitinib; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide

Ruxolitinib and Paclitaxel (12weeks)

EXPERIMENTAL

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

Drug: Ruxolitinib; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Cyclophosphamide

Interventions

Ruxolitinib 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.

Also known as: Jakafi

Paclitaxel (12weeks); Ruxolitinib and Paclitaxel (12weeks); Ruxolitinib with Paclitaxel (12weeks)

Paclitaxel DRUG

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

Also known as: Taxol

Paclitaxel (12weeks); Ruxolitinib and Paclitaxel (12weeks); Ruxolitinib with Paclitaxel (12weeks)

Doxorubicin DRUG

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

Also known as: Adriamycin

Paclitaxel (12weeks); Ruxolitinib and Paclitaxel (12weeks); Ruxolitinib with Paclitaxel (12weeks)

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Paclitaxel (12weeks); Ruxolitinib and Paclitaxel (12weeks); Ruxolitinib with Paclitaxel (12weeks)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: collaborator
• Dana-Farber Cancer Institute: lead

Study Sites (4)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 38297352 DERIVED

MeSH Terms

Conditions

Inflammatory Breast Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

ruxolitinib; Paclitaxel; Doxorubicin; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Filipa Lynce, MD, Principal Investigator
• Organization: Dana-Farber Cancer Institute

Filipa_Lynce@dfci.harvard.edu

617-632-3800

Study Officials

• Filipa Lynce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: August 9, 2016
• First Posted: August 23, 2016
• Study Start: January 24, 2018
• Primary Completion: December 31, 2022
• Study Completion: April 1, 2026
• Last Updated: February 4, 2026
• Results First Posted: April 18, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)