Phase II Study Of Combination Ruxolitinib (INCB018424) With Preoperative Chemotherapy For Triple Negative Inflammatory Breast Cancer
概览
- 阶段
- 2 期
- 干预措施
- Ruxolitinib
- 疾病 / 适应症
- Inflammatory Breast Cancer (IBC)
- 发起方
- Dana-Farber Cancer Institute
- 入组人数
- 23
- 试验地点
- 4
- 主要终点
- Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
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
详细描述
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.
研究者
Filipa Lynce, MD
Prinicipal Investigator
Dana-Farber Cancer Institute
入排标准
入选标准
- •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
- •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
排除标准
- •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.
研究组 & 干预措施
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
干预措施: Ruxolitinib
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
干预措施: Paclitaxel
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
干预措施: Doxorubicin
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
干预措施: Cyclophosphamide
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
干预措施: Ruxolitinib
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
干预措施: Paclitaxel
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
干预措施: Doxorubicin
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
干预措施: Cyclophosphamide
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
干预措施: Ruxolitinib
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
干预措施: Paclitaxel
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
干预措施: Doxorubicin
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
干预措施: Cyclophosphamide
结局指标
主要结局
Biologic Response To 7-Day Run-In Window Phase Treatment of Ruxolitinib Alone or Ruxolitinib Plus Paclitaxel
时间窗: 7 days
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.
次要结局
- Pathologic Complete Response Rate (pCR) After Preoperative Therapy(28 weeks)
- Assess Change in STAT3 Gene Expression Following run-in Treatment(7 Days)
- Changes in C-reactive Protein (CRP) Plasma Levels During Treatment(28 weeks)
- Determine Efficacy Defined as Disease-Free Survival (DFS)(2 years)
- Changes in Interleukin 6 (IL-6) Plasma Levels During Treatment(28 weeks)
- Determine Efficacy Defined as Time to Treatment Failure (TTF)(2 years)
- Determine Efficacy Defined as Overall Survival (OS)(2 years)
- Assess Residual Cancer Burden (RCB) Differences After Preoperative Therapy(28 weeks)