NCT05967884尚未招募2 期
A Randomized Phase II Window of Opportunity Clinical Trial of IL-4 +/- PD-1 Inhibition in Early-stage ER+ HER2- Breast Cancer
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Immune Cell Population Analysis
研究概览
简要总结
This proposal is for a Window of Opportunity (WOO) clinical trial using a novel combination of two Health Canada approved agents, cemiplimab (Libtayo) and dupilumab (Dupixent), for off label use in early-stage estrogen receptor positive (ER+) breast cancer.
详细描述
This is a phase II, open-label, randomized window of opportunity trial evaluating the immunologic effects within the tumour, microenvironment, and host blood of patients treated with either
- Arm A: Cemiplimab (n=10)
- Arm B: Cemiplimab + Dupilumab (n=10) administered prior to surgery. Randomization will be at 1:1 ratio in patients newly diagnosed with primary operable ER+* HER2- invasive breast cancer awaiting surgery in the next 4-6 weeks who are not planned for neoadjuvant therapy.
Primary Hypothesis: In ER+ breast cancer, blockade of IL-4 signalling using dupilumab enhances anti-tumor immunity (through reduced Th2 skewing) when used in combination with PD-1 inhibitors (Cemiplimab) compared to PD-1 inhibition alone in ER+ breast cancer
Primary Objective:
• To determine whether addition of dupilumab to cemiplimab reduces TH2 skewing of the tumor, tumor microenvironment (TME) and blood in patients with ER+ breast cancer
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female patients with newly diagnosed histologically confirmed primary invasive breast cancer currently not undergoing any treatment while awaiting surgery.
- •Invasive ductal or lobular carcinoma, invasive carcinoma Not Otherwise Specified (NOS)
- •ER+ breast cancer (1-10%*) of any size. ER positive tumor defined ≥1% positively staining cells by immunohistochemistry, according to the current American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines.
- •The participant is eligible for surgery within the next 4-6 weeks.
- •HER2/neu must be negative by immunohistochemistry (IHC) defined as IHC 0 or 1+ or fluorescence in situ hybridization (FISH) or other ISH methods with a ratio of < 2 according to current ASCO (American Society of Clinical Oncology)/CAP guidelines.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Age ≥18 years.
- •The participant (or legally acceptable representative if applicable) is able to provide written informed consent for the study.
排除标准
- •Known or suspected breast cancer metastasized to distant organ (lung, liver, bone, brain, abdomen)
- •Prior therapy with any chemotherapy or endocrine for breast cancer or other cancers within last 3 months
- •Pre-dominant histology other than invasive ductal or lobular carcinoma or invasive carcinoma NOS.
- •Patients with an active infection or an absolute neutrophil count < 1.5 x 10^9/L.
- •Patients with pre-existing renal impairment, Creatinine clearance calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of less than 50 mL/min/1.73m
- •Known or current history of pneumonitis or interstitial lung disease (e.g., idiopathic pulmonary fibrosis) or pneumonia in past month
- •Has known HIV or active Hepatitis B (e.g., HBV detected by PCR, presence of HBsAg surface antigen and/or Anti-HBc core antigen) or active Hepatitis C (e.g., HCV RNA [qualitative] is detected). Presence of Anti-HBs alone suggesting immunity to Hepatis B is eligible.
- •Any serious known immediate or delayed hypersensitivity reaction(s) to dupilumab and or cemiplimab.
- •Concurrent medical condition requiring the use of systemic immunosuppressive medications, or systemic corticosteroids at doses of greater than 10 mg Prednisone-equivalent. Topical steroids and other localized corticosteroids are permitted. Patients who have received acute, low-dose, systemic immunosuppressant medications equivalent to ≤ 10mg of prednisone within the 7 days prior to study entry (small dose of dexamethasone for nausea, short course for upper respiratory tract infection etc.) may be enrolled in the study. Use of steroids as prophylactic treatment for subjects with contrast allergies to diagnostic imaging contrast dyes will be permitted.
- •Concurrent use or planned use of any forbidden medications within 4 weeks prior to study drug administration, which include chemotherapy, immunotherapy (tumor vaccine, cytokine, or growth factor given to control cancers), other biologic therapy, investigational therapy, or hormonal therapy.
- •Confirmed pregnancy (by pregnancy test) if patient is of childbearing age or breast feeding.
- •Subjects with signs/symptoms suggestive of COVID-19 and confirmed positive COVID-19 test.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (see Appendix)
- •Any underlying medical condition that, in the Principal Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events, or renders the patient ineligible to be on study.
结局指标
主要结局
Immune Cell Population Analysis
时间窗: up to 6 months
The % change in various immune cell populations (CD3, CD8, macrophages and DC cells) in the tumor and microenvironment, Defined as the post-treatment value / pre-treatment value \* 100%
次要结局
- Study Participant Assessment of Adverse Effects(up to 6 months)
研究者
研究点 (4)
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