A Phase 2 Efficacy and Safety, Open-label, Multicenter Study of Imprime PGG® Injection in Combination With Cetuximab in Subjects With Stage IV KRAS-Mutated Colorectal Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
Study BT-CL-PGG-CRC0821 is a Phase 2, open-label, multicenter, efficacy and safety study. It will be conducted using a two-stage design with the intention of determining the initial efficacy of Imprime PGG in combination with a monoclonal antibody (MAb; cetuximab) in the treatment of KRAS-mutant colorectal cancer (CRC). Both stages will be conducted in subjects with Stage IV CRC demonstrating the KRAS gene mutation. Subjects will dose until progression of disease or discontinuation from the study for other reasons; e.g., safety, non-compliance. Approximately 56 subjects will be enrolled at three participating centers (17 into Stage 1 and 39 into Stage 2).
详细描述
Study BT-CL-PGG-CRC0821 is a Phase 2, open-label, multicenter, efficacy and safety study. It will be conducted using a two-stage design with the intention of determining the initial efficacy of Imprime PGG in combination with a monoclonal antibody (MAb; cetuximab) in the treatment of KRAS-mutant colorectal cancer (CRC). Both stages will be conducted in subjects with Stage IV CRC demonstrating the KRAS gene mutation. All subjects will receive Imprime PGG at 4 mg/kg and standard doses of cetuximab; Imprime PGG and cetuximab will be administered in 6-week cycles. Subjects will dose until progression of disease or discontinuation from the study for other reasons; e.g., safety, non-compliance. The initial cetuximab dose will be 400 mg/m2 on Cycle 1/Day1 and subsequent doses of cetuximab will be 250 mg/m2 weekly. Imprime PGG will be dosed weekly at 4 mg/kg. Tumor measurements and determination of tumor responses for this study will be performed according to RECIST. Approximately 56 subjects will be enrolled at three participating centers (17 into Stage 1 and 39 into Stage 2). Final results will be determined from combined Stage 1 and Stage 2 data.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Is >18 years old;
- •Has Stage IV carcinoma of the colon or rectum with documented histological or cytological confirmation;
- •Tumor has known KRAS mutation;
- •Has failed previous irinotecan- and oxaliplatin-containing regimens in either adjuvant or metastatic settings or is intolerant to irinotecan-based therapies;
- •Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST;
- •Has not received any other treatment for colorectal cancer within the 30 days prior to first dose of study treatment under this protocol;
- •Has an ECOG score of 0-1;
- •Has a life expectancy of > 3 months;
- •Has adequate bone marrow reserve as evidenced by:
- •ANC ≥ 1,500/μL
- •PLT ≥ 100,000/μL
- •Has adequate renal function as evidenced by serum creatinine ≤ 2.5X the upper limit of normal (ULN) for the reference lab;
- •Has adequate hepatic function as evidenced by:
- •AST ≤ 3X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
- •ALT ≤ 3X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
- •Bilirubin < 1.5 mg/dl, OR direct bilirubin < 1.0 mg/dl
- •Serum Albumin > 3.0 gm/dl
- •Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC); and
- •If the subject is a woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 60 days following the last dose of study medication (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method).
排除标准
- •Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
- •Has a known hypersensitivity to baker's yeast or has an active yeast infection;
- •Has had previous exposure to Betafectin® or Imprime PGG;
- •Has an active, uncontrolled infection;
- •Has known or suspected brain metastases;
- •Had a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia or curatively-treated prostate cancer with a PSA of < 2.0 ng/mL;
- •Has known HIV/AIDS, Hepatitis B, Hepatitis C, connective tissue disease, or other clinical diagnosis, ongoing or intercurrent illness that in the investigator's opinion should prevent participation;
- •If female, is pregnant or breast-feeding;
- •Is receiving concurrent standard and/or investigational anti-cancer therapy or has received such therapy within a period of 30 days prior to the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory-authority-approved indication); or
- •Has previously received an organ or progenitor/stem cell transplant.
结局指标
主要结局
Objective response rate (ORR)
时间窗: Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
次要结局
- Disease control rate (DCR) and duration of disease control(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Complete response (CR), partial response (PR), and stable disease (SD) rates(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Duration of objective tumor response(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Duration of stable disease(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Time to progression (TTP)(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Progression-free survival (PFS)(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Safety of the dosing regimen(Assessed after 17 subjects complete 1 treatment cycle and at completion of study.)
- Overall survival(Assessed after all subjects are deceased or lost to follow-up)