PM-01: Phase 1b Study of PGG Beta Glucan (Imprime PGG®) in Combination With Anti-MUC1 Antibody (BTH1704) and Gemcitabine (Gemzar®) for the Treatment of Advanced Pancreatic Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This Phase Ib dose escalation study will evaluate BTH1704, a monoclonal antibody that targets an aberrantly glycosylated antigen Mucin 1, and Imprime PGG, a glucan contained in yeast that is essential in triggering a leukocyte-mediated cytotoxic response towards tumor cells, in combination with gemcitabine in patients with advanced PDAC. The three intravenous drugs are taken in tandem 4 times in a 28-day cycle. The MAD of BTH1704 (BTH, 3 dose levels) in combination with gemcitabine (Gem) and Imprime PGG (I) will be determined using a standard "3+3" design. Treatment continues until disease progression, unacceptable toxicity, physician discretion, or patient refusal.
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
- •Male or female ≥ 18 years
- •Histologically or cytologically confirmed adenocarcinoma of the pancreas, including pancreatic adenosquamous carcinoma, pancreatic anaplastic adenocarcinoma, pancreatic signet ring carcinoma, papillary mucinous carcinoma, acinar cell carcinoma, and ampulla of vater carcinoma,that is locally advanced (not able to proceed with surgery), recurrent, or metastatic (mixed adenocarcinoma of the pancreas is acceptable where the invasive component is predominantly adenocarcinoma)
- •Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1
- •Has an ECOG PS of 0, 1, or 2
- •Has been off chemotherapy for > or = 2 weeks
- •Has a patent biliary stent if required for biliary ductal obstruction, has adequate nutritional intake, and pain which is stable for a minimum of 24 hrs (pain score ≤ 3/10)
- •Has total bilirubin < 2 mg/dL, AST and ALT < 3.0 × ULN or < 5 x ULN for subjects with known hepatic metastases
- •Has serum creatinine < 2.5 × ULN
- •Has hemoglobin ≥ 9 g/dL, ANC ≥ 1.0 × 10^9/L, and platelet count ≥ 100 × 10^9/L
- •Must be willing and able to comply with study
- •Has read, understood and signed the ICF
- •Women of childbearing potential must not be pregnant or breast-feeding. In addition, a medically acceptable method of birth control must be used or total abstinence. Women who are postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) are not considered to be WOCP.
- •Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male patients with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms at least 30 days after the last dose of study drug. Total abstinence is an acceptable alternative.
- •Prior systemic treatments for metastatic disease are permitted, including targeted therapies, biologic response modifiers, chemotherapy, hormonal therapy, or investigational therapy.
- •Availability of tissue if applicable (from the primary tumor or metastases)for banking
- •Willingness to donate blood for biomarker studies
- •Must have received at least one prior systemic chemotherapy on which disease progressed
排除标准
- •Has a diagnosis of resectable pancreatic adenocarcinoma
- •Had surgery within 4 weeks prior to study treatment
- •Has either untreated or symptomatic CNS mets
- •Has a known hypersensitivity to BTH1704, murine proteins, or any component of BTH1704
- •Has a known hypersensitivity to baker's yeast
- •Has had previous exposure to Imprime PGG
- •Has previously received an organ or progenitor/stem cell transplant
- •Has a history of blood clots, pulmonary embolism, or DVT unless controlled by anticoagulant treatment
- •Has a known history of HIV positivity or untreated & uncontrolled hepatitis B or C
- •Has any clinically significant infection
- •Has any other severe, uncontrolled medical condition, including uncontrolled DM or unstable CHF or has a known or suspected allergy to the study drug
- •Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation
- •Presence of any non-healing wound, fracture, or ulcer
- •Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance
- •Has any mental or medical condition that prevents the patient from giving informed consent
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to gemcitabine or drugs to formulate.
研究组 & 干预措施
IMPRIME PGG, BTH1704, & Gemcitabine
Imprime PGG with BTH1704 at assigned doses administered on days 1, 8, 15, and 22 of a 28-day cycle with Gemcitabine on days 1, 8, and 15, at assigned doses, of a 28-day cycle.
干预措施: BTH1704 (Drug)
IMPRIME PGG, BTH1704, & Gemcitabine
Imprime PGG with BTH1704 at assigned doses administered on days 1, 8, 15, and 22 of a 28-day cycle with Gemcitabine on days 1, 8, and 15, at assigned doses, of a 28-day cycle.
干预措施: IMPRIME PGG (Drug)
IMPRIME PGG, BTH1704, & Gemcitabine
Imprime PGG with BTH1704 at assigned doses administered on days 1, 8, 15, and 22 of a 28-day cycle with Gemcitabine on days 1, 8, and 15, at assigned doses, of a 28-day cycle.
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Up to 30 days post last dose
The primary objective of this Phase 1b study is to determine the maximal administered dose (MAD) of BTH1704 (Mucin-1 targeted antibody) in combination with gemcitabine and Imprime PGG (beta 1,3/1,6 glucan) when given to patients with advanced and previously treated pancreatic ductal adenocarcinoma (PDAC).
次要结局
- Disease Response based on RECIST Criteria(Up to 8 weeks following final dose.)
- Adverse Effects(Up to 30 days post final dose)
研究者
Howard Ozer
Professor
University of Illinois at Chicago