A Phase 1b, Safety, PK, and Efficacy, Multicenter, Dose-Escalating Study of Imprime PGG in Combination With Cetuximab With and Without Irinotecan Therapy in Patients With Recurrent/Progressive Colorectal Carcinoma Following Treatment With a 5-FU Regimen.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Safety and Maximum Tolerated Dosage of Imprime PGG When Used in Combination With Cetuximab With or Without Irinotecan Therapy
研究概览
简要总结
Phase 1b, safety, pharmacokinetic, and efficacy, multicenter, dose-escalating Study of Imprime PGG™ Injection dosed in combination with Cetuximab and concomitant irinotecan therapy. Enrolled patients will have a confirmed diagnosis of recurrent or progressive colorectal carcinoma following treatment with a 5-fluorouracil-containing regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is between the ages of 18 and 75 years old, inclusive;
- •Has a recurrent or progressive carcinoma of the colon or rectum with documented histological confirmation of primary carcinoma;
- •Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST;
- •Has previously received treatment with 5-FU, alone or in combination with other anti-tumor medications (except as in exclusion #1 below); Prior treatment with capecitabine (Xeloda®) will be considered to fulfill the requirement for prior treatment with 5-FU;
- •Has a Karnofsky Score of ≥ 70;
- •Has a life expectancy of > 3 months;
- •Has adequate bone marrow reserve as evidenced by:
- •ANC ≥ 1,500/μL
- •PLT ≥ 100,000/μL
- •HGB ≥ 9 g/dl;
- •Has adequate renal function as evidenced by serum creatinine ≤ 1.5X the upper limit of normal (ULN) for the reference lab;
- •Has adequate hepatic function as evidenced by:
- •Serum total bilirubin ≤ 1.0 mg/dL
- •AST ≤ 3X ULN for the reference lab (≤ 5X ULN for patients with known hepatic metastases)
- •ALT ≤ 3X ULN for the reference lab (≤ 5X ULN for patients with known hepatic metastases);
- •Has discontinued any CYP3A4 enzyme-inducing anticonvulsants (such as phenytoin, phenobarbital or carbamazepine) and antimicrobials (such as refampin and rifabutin), St. John's Wort, and ketoconasole at least two weeks prior to Day 1
- •Has recovered from the effects of any prior surgery, radiotherapy, or chemotherapy;
- •Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC); and
- •If a woman of childbearing potential or a fertile man (and his partners), must agree to use an effective form of contraception during the study and for 120 days following the last dose of study medication (an effective form of contraception is an hormonal contraceptive or a double-barrier method).
排除标准
- •Has previously received treatment with cetuximab or irinotecan;
- •Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
- •Has a hereditary fructose intolerance;
- •Has a known hypersensitivity to baker's yeast, or has an active yeast infection;
- •Has had previous exposure to Betafectin® or Imprime PGG;
- •Has received previous radiation therapy to >30% of active bone marrow;
- •Has a fever of >38.5º C within 3 days prior to initial dosing;
- •Has known or suspected central nervous system (CNS) 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 or autoimmune disease, or other clinical diagnosis, ongoing or intercurrent illness that in the investigator's opinion would prevent participation;
- •If female, is pregnant or breast-feeding;
- •Is receiving concurrent investigational therapy or has received investigational 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.
研究组 & 干预措施
Imprime PGG 2mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Imprime PGG 2 mg/kg (Biological)
Imprime PGG 2mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Cetuximab (Biological)
Imprime PGG 2mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Irinotecan (Drug)
Imprime PGG 4mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Imprime PGG 4 mg/kg (Biological)
Imprime PGG 4mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Cetuximab (Biological)
Imprime PGG 4mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Irinotecan (Drug)
Imprime PGG 6mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Cetuximab (Biological)
Imprime PGG 6mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Irinotecan (Drug)
Imprime PGG 6mg/kg+Cetuximab+Irinotecan
Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
干预措施: Imprime PGG 6mg/kg (Biological)
Imprime PGG 2mg/kg+Cetuximab
Treatment Arm 2 2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
干预措施: Imprime PGG 2 mg/kg (Biological)
Imprime PGG 2mg/kg+Cetuximab
Treatment Arm 2 2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
干预措施: Cetuximab (Biological)
Imprime PGG 4mg/kg+Cetuximab
Treatment Arm 2 4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
干预措施: Imprime PGG 4 mg/kg (Biological)
Imprime PGG 4mg/kg+Cetuximab
Treatment Arm 2 4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
干预措施: Cetuximab (Biological)
Imprime PGG 6mg/kg+Cetuximab
Treatment Arm 2 6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
干预措施: Cetuximab (Biological)
Imprime PGG 6mg/kg+Cetuximab
Treatment Arm 2 6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
干预措施: Imprime PGG 6mg/kg (Biological)
结局指标
主要结局
Safety and Maximum Tolerated Dosage of Imprime PGG When Used in Combination With Cetuximab With or Without Irinotecan Therapy
时间窗: From the date of the first dose of study drug to disease progression or until development of a drug toxicity that precludes further protocol treatment, up to 15 months
Safety and maximum tolerated dosage (MTD) of Imprime PGG was determined by the Adverse Events Task Force based on the drug-related adverse events experienced by subjects that met the criteria for a dose limiting toxicity (DLT) within a timeframe of the first 3 weeks of treatment and 1 week follow-up. If one in the initial three subjects for a dose group experienced a DLT, three additional subjects were enrolled in that dose group. If two or more subjects in the expanded dose group experienced a DLT, the study was to be stopped and the MTD was defined as the dose prior to the dose at which the DLT was observed. If a DLT occurred in the first dose group (2 mg/kg Imprime PGG), the protocol allowed for the next group to be dosed at a reduced dose of 1 mg/kg Imprime PGG. The dose groups described above were: Dose Group 1 (Imprime PGG 2 mg/kg), Dose Group 2 (Imprime PGG 4 mg/kg), Dose Group 3 (Imprime PGG 6 mg/kg).
次要结局
- Rate of Number of Participants With Tumor Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) in Each Study Arm(From the date of the first dose of study drug to disease progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months)
- Overall Response Rate (ORR) Per RECIST Criteria v1.0 in Each Study Arm(From the date of the first dose of study drug to disease progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months)
- Disease Control Rate (DCR) Per RECIST Criteria v1.0 in Each Study Arm(From the date of the first dose of study drug to disease progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months)
- Duration of Time-to-Progression (TTP) in Each Study Arm(The time from the date of the first dose of study drug to the date of the first documented progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months)
- Duration of Overall Tumor Response in Each Study Arm(The time from the date of the first dose of study drug to the date of the first documented progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months)
- Duration of Disease Control in Each Study Arm(The time from the date of first dose of study drug to the date of first documented progression, or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months)