Clinical Trials /

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

NCT02876302

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Study Of Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer
  • Official Title:Phase II Study Of Combination Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 16-151
  • NCT ID: NCT02876302

Trial Conditions

  • Inflammatory Breast Cancer (IBC).

Trial Interventions

DrugSynonymsArms
RuxolitinibJakafiPaclitaxel (12weeks)
PaclitaxelTaxolPaclitaxel (12weeks)
DoxorubicinAdriamycinPaclitaxel (12weeks)
CyclophosphamideCytoxanPaclitaxel (12weeks)

Trial Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Paclitaxel (12weeks)ExperimentalPaclitaxel 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
  • Ruxolitinib
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide
Ruxolitinib with Paclitaxel (12weeks)ExperimentalPaclitaxel 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
  • Ruxolitinib
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide
Ruxolitinib and Paclitaxel (12weeks)ExperimentalPaclitaxel 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
  • Ruxolitinib
  • Paclitaxel
  • Doxorubicin
  • Cyclophosphamide

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 (defined as IHC 0 or 1+, or FISH ratio <2.0).

- Patients must have the clinical diagnosis of inflammatory breast cancer as evidenced by the onset of signs and symptoms noted below within a 6 month time-period:

- Erythema of the breast

- Edema of the skin of the breast

- Enlargement of the 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

- Total bilirubin within normal institutional limits

- AST (SGOT)/ALT (SGPT) < 2.5 X institutional upper limit of normal

- Creatinine between 0-1.3 mg/dL OR creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal

- Patients must be without evidence of visceral or bone involvement with metastatic cancer on physical exam or any diagnostic study. Extensive nodal involvement is allowed.

- 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.

- Patients with evidence of metastatic disease involvement in viscera or bone.

- 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.

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Both
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assess JAK Inhibition With Ruxolitinib On pStat3+ Expression
Time Frame:7 days
Safety Issue:No
Description:Comparison of JAK expression in pretreatment biopsy specimens to post-Ruxolitinib run-in (after 7 days of Ruxolitinib alone or with one dose of weekly paclitaxel) biopsy specimens.

Secondary Outcome Measures

Measure:Determine Pathologic Complete Response rate (pCR) after preoperative therapy
Time Frame:28 weeks
Safety Issue:No
Description:pCR defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
Measure:Correlate effects on pSTAT3+ and STAT3 gene expression with pCR
Time Frame:28 weeks
Safety Issue:No
Description:assess pSTAT level and gene expression on pre-treatment tumor biopsy specimens and correlate expression with pCR
Measure:Assess changes in pSTAT3 level and STAT3 gene expression following treatment
Time Frame:28 weeks
Safety Issue:No
Description:assess pSTAT level and gene expression on pre-treatment tumor biopsy
Measure:Asses difference in pCR rate following preoperative treatment
Time Frame:28 weeks
Safety Issue:No
Description:pCR defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative therapy.
Measure:Determine efficacy defined as Disease-Free Survival (DFS)
Time Frame:5 years
Safety Issue:No
Description:Defined as time of surgery until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast.
Measure:Determine efficacy defined as Time to Treatment Failure (TTF)
Time Frame:5 years
Safety Issue:No
Description:Defined as time of treatment initiation until occurrence of recurrence, contralateral cancer, death attributable to any cause, second primary cancer other than breast or occurrence of progressive disease during preoperative therapy or treatment of disease that is not surgically resectable.
Measure:Determine efficacy defined as Overall Survival (OS)
Time Frame:5 years
Safety Issue:No
Description:Defined as time from surgery until death from any cause or from treatment initiation until death from any cause
Measure:Assess residual Cancer Burden (RCB) differences after preoperative therapy
Time Frame:5 years
Safety Issue:No
Description:
Measure:Describe changes in IL-6 plasma levels during treatment
Time Frame:5 years
Safety Issue:No
Description:IL-6 levels will be recorded in the case report forms.
Measure:Describe changes in CRP plasma levels during treatment
Time Frame:5 years
Safety Issue:No
Description:CRP levels will be recorded in the case report forms.
Measure:Assess distribution of CD44+/CD24- stem cell population in tumor pre- and post-exposure to ruxolotinib
Time Frame:5 years
Safety Issue:No
Description:Performed on breast biopsies and residual disease in mastectomy specimens
Measure:Assess pSTAT level and STAT3gene expression when ruxolitinib is withdrawn
Time Frame:5 years
Safety Issue:No
Description:assess pSTAT level and gene expression on pre-treatment tumor biopsy specimen, run-in biopsy specimen, and any residual tumor at time of surgical resection
Measure:Asses pSTAT3 level and STAT3 gene expression after combination ruxolitinib with paclitaxel
Time Frame:5 years
Safety Issue:No
Description:assess pSTAT level and gene expression on tumor biopsy specimens

Trial Keywords

  • Inflammatory Breast Cancer
  • Breast Cancer
  • Triple Negative Breast Cancer