NCT02907099已完成2 期
A Phase IIb Pilot Study to Assess the Efficacy, Safety, and Pharmacodynamics Effects of Pembrolizumab and BL-8040 in Patients With Metastatic Pancreatic Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall Response Rate
研究概览
简要总结
This pilot phase IIb trial studies how well pembrolizumab and CXCR4 antagonist BL-8040 work in treating patients with pancreatic cancer that has spread to other places. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. CXCR4 antagonist BL-8040 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and CXCR4 antagonist BL-8040 may work better in treating patients with pancreatic cancer.
详细描述
PRIMARY OBJECTIVES:
I. To assess the overall response rate (complete response or partial response) after treatment with CXCR4 antagonist BL-8040 (BL-8040) and pembrolizumab.
SECONDARY OBJECTIVES:
I. To determine the ability of BL-8040 by itself and in combination with pembrolizumab to increase T cell infiltration into the tumor.
II. To determine if BL-8040 treatment results in increases in circulating immune cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report
- •Be willing and able to provide written informed consent for the trial
- •Have measurable disease based on RECIST 1.1; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- •Have documented objective radiographic progression after stopping treatment with first-line therapy; Note: the same image acquisition and processing parameters should be used throughout the study for a given subject
- •Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion from a metastatic site; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from Merck; the specimen must be from a biopsy site that would be accessible for at least one subsequent biopsy after initiation on the trial
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- •Have a predicted life expectancy of greater than 3 months
- •Absolute neutrophil count (ANC) >= 1,000 /mcL (performed within 10 days of treatment initiation)
- •Platelets >=100,000 /mcL (performed within 10 days of treatment initiation)
- •Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 14 days of assessment) (performed within 10 days of treatment initiation)
- •Serum creatinine OR measured or calculated creatinine clearance (should be calculated per institutional standard) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 X upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels =< 1.5 X institutional ULN (performed within 10 days of treatment initiation)
- •Serum total bilirubin =< ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > ULN (performed within 10 days of treatment initiation)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 1.5 X ULN (performed within 10 days of treatment initiation)
- •Albumin >= 3.3 mg/dL in the absence of dehydration (performed within 10 days of treatment initiation)
- •International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
- •Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
- •Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (cycle 1, day 1) (female subjects of childbearing potential); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- •Female subjects of childbearing potential must be willing to use an adequate method of contraception; contraception, for the course of the trial through 120 days after the last dose of trial drug; note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject; male subjects of childbearing potential must agree to use an adequate method of contraception; contraception, starting with the first dose of trial therapy through 120 days after the last dose of trial therapy
排除标准
- •Has pancreatic tumor other than adenocarcinoma, including: acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma; vater and periampullary duodenal or common bile duct malignancies
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigation device within 4 weeks of the first dose of treatment
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- •Had a solid organ or hematologic transplant
- •Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- •Has a diagnosed additional malignancy within 1 year prior to first dose of study treatment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers
- •Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by principal investigator (PI) and radiology review
- •Subjects excluded if there is a history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease, or active, non-infectious pneumonitis
- •Has an active infection requiring systemic therapy
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
- •Has received prior immunotherapy with agents that target PD-1, PD-L1, PD-L2, CTLA-4, OX-40, or CD-137 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
- •Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- •Has known hepatitis B or hepatitis C
- •Has received a live vaccine within 30 days of planned start of study therapy (cycle 1, day 1); Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
- •Has a known history of active TB (Bacillus tuberculosis)
- •Unable to tolerate a contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) for staging/restaging purposes
- •Hypersensitivity to pembrolizumab or any of its excipients
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to such agents administered more than 4 weeks earlier
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered small molecule agent; a. Note: subjects with =< grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study; b. Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- •Patients requiring beta blockade are disqualified from participating in this study
- •Patients who, in the estimation of the treating physician or primary investigator, have had a clinical deterioration of their ECOG performance within the month prior to enrollment
- •The use of natural or synthetic cannabinoids
- •Patients with unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, and current congestive heart failure New York Heart Association class III or higher
研究组 & 干预措施
Treatment (CXCR4 antagonist BL-8040, pembrolizumab)
Experimental
Patients receive CXCR4 antagonist BL-8040 SC on days 1-5 and 8-12 of cycle 1 and days 1, 4, 8, and 11 of subsequent cycles. Beginning cycle 2, patients also receive pembrolizumab IV over about 30 minutes on day 1. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: CXCR4 Antagonist BL-8040 (Drug)
Treatment (CXCR4 antagonist BL-8040, pembrolizumab)
Experimental
Patients receive CXCR4 antagonist BL-8040 SC on days 1-5 and 8-12 of cycle 1 and days 1, 4, 8, and 11 of subsequent cycles. Beginning cycle 2, patients also receive pembrolizumab IV over about 30 minutes on day 1. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Pembrolizumab (Biological)
Treatment (CXCR4 antagonist BL-8040, pembrolizumab)
Experimental
Patients receive CXCR4 antagonist BL-8040 SC on days 1-5 and 8-12 of cycle 1 and days 1, 4, 8, and 11 of subsequent cycles. Beginning cycle 2, patients also receive pembrolizumab IV over about 30 minutes on day 1. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
结局指标
主要结局
Overall Response Rate
时间窗: 3 years
To assess the overall response rate (complete response or partial response) PER RECIST 1.0 after treatment with CXCR4 antagonist BL-8040 (BL-8040) and pembrolizumab
次要结局
- Quantity of T-Cell Infiltration Pre-treatment and Post Treatment Following Administration of BL-8040 by Itself and BL-8040 With Pembrolizumab(pre treatment at baseline and post treatment (2 months))
- Quantity of Circulating T-Cells Pre-treatment and Post Treatment Following Administration of BL-8040(pre treatment and post treatment, up to 3 years)
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0(2 years)
研究者
研究点 (1)
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