A Multicenter, Open-Label, Three-Part Study to Evaluate the Safety and Effectiveness of Immunopheresis With Immunicom's LW-02 Device in Removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) as Well as Clinical Efficacy in Treatment of Patients With Advanced, Refractory Breast Cancer (BC) Alone, or in Combination With Low Dose Chemotherapy Versus Low Dose Chemotherapy.
试验速览
- 阶段
- 1 期
- 入组人数
- 170
- 试验地点
- 5
- 主要终点
- Safety and Tolerability Assessment
研究概览
简要总结
This is a multicenter, open-label, Phase 1/ 2 study to evaluate the short-term and longer-term safety, tolerability, and effectiveness of Immunopheresis® with the LW-02 column in removal of Soluble Tumor Necrosis Factor Receptors (sTNF-Rs) from plasma of patients with advanced, refractory Breast Cancer (BC) and for disease control when employed as monotherapy, or in combination with a low dose chemotherapy. A low dose chemotherapy will serve as control.
详细描述
This is a multicenter, open-label, Phase 1/ 2 study to evaluate the short-term and longer-term safety, tolerability, and effectiveness of Immunopheresis® with the LW-02 column in removal of sTNF-Rs from plasma of patients with advanced, refractory BC and for disease control when employed as monotherapy, or in combination with a low dose chemotherapy. A low dose chemotherapy will serve as control.
Part A (n=10 evaluable patients): Overall safety, tolerability, and sTNF-R-removal effectiveness of LW-02 device-based immunopheresis monotherapy conducted 3 times per week for 4 weeks in patients with advanced TNBC. This part is already completed.
Part B/Part B Extension (n = up to 30 evaluable patients): Overall safety, tolerability, and sTNF-Rs-removal effectiveness of LW-02 device-based Immunopheresis® 3 times per week for up to 16 weeks combined with low dose chemotherapy in patients with advanced refractory BC..
Part C (3 treatment arms; n=50 patients per treatment arm): Randomized comparison of overall safety, tolerability, and clinical efficacy effectiveness of (i) Immunopheresis® monotherapy with the LW-02 column 3 times per week for 16 weeks, (ii) or Immunopheresis® in combination with low dose chemotherapy, and (iii) plain low dose chemotherapy.
Safety Endpoints
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form
- •Age ≥ 18 years female
- •Able to comply with the study protocol in the investigator's judgment
- •Histologically confirmed diagnosis of BC
- •Inoperable locally-advanced or metastatic disease
- •Must be able to provide archival pathological material from primary or metastatic site (formalin-fixed paraffin embedded [FPPE] tissue block) for central BC confirmation and verification of BC subtype and tmTNF expression
- •Weight ≥ 35 kg
- •Life expectancy of at least 3 months with malignancy; expected to live for one year without malignancy.
- •Adequate organ function:
- •Hemoglobin ≥ 9.5g/dL (may be achieved with transfusion support)
- •Absolute Granulocyte Count (ANC) ≥1.5 × 109/L (without granulocyte colony- stimulating factor support within 2 weeks prior to the first study treatment)
- •Platelets (PTL) ≥ 100 × 109/L
- •AST/ALT ≤2.5× ULN (patients with documented liver metastases: AST and/or ALT ≤ 5 × ULN; patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 ×ULN)
- •Serum creatinine (S-Cr) ≤ 1.5
- •Albumin ≥ LLN
- •Bilirubin ≤ 1.5 ULN
- •International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. This applies only to patients who are not receiving therapeutic anticoagulation agents.
- •Patients receiving therapeutic anticoagulation agents must be on a stable dose
- •Calcium level within normal ranges.
- •The last dose of prior systemic anticancer therapy must have been administered ≥ 7 days prior to study treatment initiation
- •Measurable disease, as defined by RECIST v1.1
- •ECOG performance status 0, 1 or
- •Patients with asymptomatic CNS metastases (treated or untreated), as determined by CT or MRI evaluation during screening and prior radiographic evaluation, are eligible.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use double barrier contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of chemotherapy.
- •Patients must have recovered (i.e., improvement to Grade 1 or better) from all acute toxicities from previous therapy, excluding alopecia. If a patient was previously treated with taxanes, the patient must have recovered from any adverse effects or remain at an acceptable level for patient (i.e. peripheral neuropathy).
排除标准
- •Symptomatic CNS metastases
- •Subjects with brain metastases at screening must have clinically controlled neurologic symptoms and have received previous adequate treatment, defined as surgical excision and/or radiation therapy with stable neurologic function and no evidence of CNS disease progression as determined by comparing a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan performed during screening to a prior scan performed at least 4 weeks earlier and provided that the subject is asymptomatic, has no evidence of cavitation or hemorrhage, and does not require corticosteroids;
- •Leptomeningeal disease
- •Uncontrolled pericardial effusion or ascites requiring recurrent drainage procedures
- •Pregnant or lactating or intending to become pregnant during the study - women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-drug-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 2 weeks prior to initiation of study treatment
- •Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
- •Significant cardiovascular disease, such as New York Heart Association cardiac disease ≥ Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina
- •Patients with known coronary artery disease or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
- •Patient with known persistent, uncontrolled hypotension
- •Significant renal disorder requiring dialysis or indication for renal transplant
- •Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to study treatment initiation
- •Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- •Fever, or any active immunosuppressive systemic infection including history of human immunodeficiency virus (HIV) infection
- •Other serious diseases (e.g., life expectancy less than 3 months) including active second malignancy except for basal cell carcinoma or cervical carcinoma in situ
- •Active infection
- •Patients in whom vascular access is not considered achievable
- •Use of any standard high dose or low dose chemotherapy or immunosuppressive therapies and or standard radiation therapy concurrently as well anticipated need for any of the former during the study
- •Body mass index (BMI) ≥ 35 kg/m2
- •Any condition that the patient's physician determines to be detrimental to the patient participating in this study; including any clinically important deviations from normal clinical laboratory values or concurrent medical events.
- •Inability to understand the local language for use of the patient QOL instruments (EQ-5D-5L and others).
研究组 & 干预措施
Immunopheresis® - Arm 1
All patients will receive up to 16 weeks of initial treatment as per study arm assignment, which will include up to 48 LW-02 column-based Immunopheresis® treatments over a 4-month period (up to 3 procedures per week) though treatment can be extended based on certain protocol-specfied conditions. Each patient assigned to the treatment with LW-02 column-based Immunopheresis® will require central vascular access for the procedure. This part is alrady completed.
干预措施: Plasma soluble TNF receptor pulldown (Other)
Immunopheresis® combined with low dose chemotherapy - Arm 2
All patients will receive up to 16 weeks of treatment as per study arm assignment, which will include up to 48 LW-02 column-based Immunopheresis® treatments over a 4-month period (up to 3 procedures per week) though treatment can be extended based on certain protocol-specfied conditions. Each patient will require central vascular access for the procedure. Patients also will receive a low dose chemotherapy regimen administered iv or oraly. Patients treated with combination will be administered their chemotherapy following the first LW-02 column-based Immunopheresis® procedure of each week starting from week 2, assuming first week of study treatment serves as a run-in period confirming good tolerance of Immunopheresis® alone.
干预措施: Plasma soluble TNF receptor pulldown + chemotherapy (Other)
Chemotherapy - Arm 3
Patients who are assigned chemotherapy arm of the study will be treated with low dose chemotherapy alone. The chemotherapy will be administered intravenously or oraly depending on the regimen used.
干预措施: Chemotherapy Drugs, Cancer (Drug)
结局指标
主要结局
Safety and Tolerability Assessment
时间窗: 16 weeks
Safety and tolerability assessment based on adverse event / serious adverse event (AE / SAE) and adverse device / serious adverse device effects (ADE / SADE) reporting using CTCAE/MedDRA coding terms
Safety endpoints of special interest assessment
时间窗: 16 weeks
Incidence of tumor lysis syndrome and systemic inflammatory response syndrome.
Clinical endpoint - overall survival
时间窗: 16 weeks
A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Overall Survival (OS). Overall survival ( OS ) is defined as the time from randomization to death from any cause, is adirect measure of clinical benefit to a patient.
Clinical endpoint - progression free survival
时间窗: 16 weeks
A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Progression Free Survival (PFS) Progression-free survival ( pfs ) is defined as time from randomization until firstevidence of tumour progression or until death from any cause, whichever comes first.
Clinical endpoint - disease control rate
时间窗: 16 weeks
A series of secondary efficacy outcome measures will be evaluated based on overall survival from the date of the firststudy treatment and changes in objective response using RECIST (1.1) or iRECIST criteria. The assessed parameterswill be:Disease Control Rate (DCR) Overall response rate (ORR) is defined as the proportion of patients who have a partialor complete response to therapy; it does not include stable disease and is a direct measure of drug tumoricidal activity.In contrast, disease control rate is a composite of ORR and stable disease and is useful to measure the efficacy oftherapies that have tumoristatic effects rather than tumoricidal effects.
Soluble Tumor Necrosis Factor Receptor (sTNFR) concentrations in plasma (picogram per mL)
时间窗: 16 weeks
Column efficiency and effectiveness in removal of sTNF-Rs from patient plasma without clinically-meaningful leaching of capture ligand (SC-TNF-α) - change in sTNF-R and TNF-α plasma levels from initiation to the end of each immunopheresis procedure, including pre- and post-column measurements, between each treatment, and from baseline to end of a treatment cycle (4 weeks - Part A and B, or 16 weeks - Part C).
次要结局
- Patient functioninig with Eastern Cooperative Oncology Group (ECOG)(16 weeks)
- Quality-of-life (QoL) Assessment with EQ-5D-5L scale(16 weeks)
- Quality-of-life (QoL) Assessment with EORTC-QLQ-C30 scale(16 weeks)
- Quality-of-life (QoL) Assessment with EORTC: QLQ-BR23(16 weeks)
- Muscle performance assessment with a hand grip test(16 weeks)
- Nutritional status(16 weeks)
- Physical performance status assessment with 6 minute walk test (6MWT)(16 weeks)