A Phase I Study of VTX-2337 in Combination With Pegylated Liposomal Doxorubicin (PLD; NSC# 712227) or in Combination With Weekly Pactilaxel (NSC #673089) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 10
- 主要终点
- First-cycle dose-limiting toxicities
研究概览
简要总结
This phase I trial is studying the side effects and best dose of TLR8 agonist VTX-2337 and pegylated liposomal doxorubicin hydrochloride in treating patients with recurrent or persistent ovarian epithelial, fallopian tube, or peritoneal cavity cancer. Biological therapies, such as TLR8 agonist VTX-2337, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving TLR8 agonist VTX-2337 together with pegylated liposomal doxorubicin hydrochloride or paclitaxel may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated doses (MTD) and dose limiting toxicities (DLTs) of VTX-2337 when administered in combination with pegylated liposomal doxorubicin (PLD; Doxil, Lipodox™) 40 mg/m2 in Regimen 1 and when administered in combination with weekly paclitaxel 80 mg/m2 in Regimen 2, and the associated DLTs based on adverse events that occur in cycle 1 for each of these combinations in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
II. To examine the tolerability of the combination at the MTD of VTX-2337 assessed in combination with PLD 40 mg/m2 and with PLD 50 mg/m2 in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
III. To determine recommended phase II doses (RP2D) of VTX-2337 in combination with PLD in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
SECONDARY OBJECTIVES:
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma
- •Histologic documentation of the original primary tumor is required via the pathology report
- •Patients with the following histologic cell types are eligible:
- •Serous adenocarcinoma
- •Endometrioid adenocarcinoma
- •Mucinous adenocarcinoma
- •Undifferentiated carcinoma
- •Clear cell adenocarcinoma
- •Mixed epithelial adenocarcinoma
- •Transitional cell carcinoma
- •Malignant Brenner tumor
- •Adenocarcinoma not otherwise specified (N.O.S.)
- •Patient must have measurable disease or detectable (non-measurable) disease:
- •Measurable disease will be defined by RECIST 1.1
- •Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded)
- •Each lesion must be ≥ 10 mm when measured by CT, MRI, or caliper measurement by clinical exam or ≥ 20 mm when measured by chest x-ray
- •Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI
- •Detectable (non-measurable) disease is defined as not having measurable disease but has at least one of the following conditions:
- •Baseline values of CA-125 ≥ 2 x ULN
- •Patients whose CA-125 is < 100 U/mL must undergo a second confirmatory value within a period of ≤ 4 weeks
- •Patients with a level ≥ 100 U/mL may be entered without confirmatory measurement
- •The CA-125 assessment for eligibility must be done at least 4 weeks after paracentesis or other surgical procedures
- •Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions
- •Patient with measurable disease must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1
- •Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
- •Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents or extended therapy administered after surgical or non-surgical assessment
- •For patients enrolled in Regimen 2, weekly paclitaxel, treatment for their primary disease must have included paclitaxel; this can have been given weekly or every 3 weeks; patients who experienced severe hypersensitivity to paclitaxel are excluded
- •Patients are allowed to receive, but are not required to receive, two additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum, non-taxane regimen
- •For patients enrolled in Regimen 1 which includes PLD, prior treatment with PLD is NOT allowed
- •For patients enrolled in Regimen 2 which includes weekly paclitaxel, prior treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed
- •Patients are allowed to receive, but are not required to receive, non-cytotoxic therapy (such as bevacizumab) as part of their primary treatment regimen; patients are allowed to receive, but are not required to receive, non-cytotoxic therapy for management of recurrent or persistent disease
- •Patients who have received only one prior cytotoxic regimen (platinum-based regimen for management of primary disease), must have a platinum-free interval of less than 12 months, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy
- •No patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage within six months of the first date of treatment on this study
- •No patients who have received oral or parenteral corticosteroids within 2 weeks of study entry or who require ongoing systemic immunosuppressive therapy for any reason
- •Patients must have a GOG performance status of 0 or 1
- •Absolute neutrophil count (ANC) ≥ 1,500/mm^3; this ANC cannot have been induced or supported by granulocyte colony-stimulating factors
- •Platelets ≥ 100,000/mm^3
- •Hemoglobin ≥ 9 g/dL
- •Creatinine ≤ 1.5 x institutional upper limit normal (ULN)
- •Bilirubin ≤ 1.5 x ULN
- •SGOT (AST) ≤ 3.0 x ULN
- •Alkaline phosphatase ≤ 2.5 x ULN
- •Neuropathy (sensory and motor) less than or equal to grade 1
- •Not pregnant or nursing
- •Negative pregnancy test
- •Patients of childbearing potential must be practicing an effective form of contraception
- •Patients should be free of active infection requiring parenteral antibiotics
- •No patients with active autoimmune disease
- •"Active" refers to any condition currently requiring therapy
- •Examples of autoimmune disease include systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis
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排除标准
- 未提供
研究组 & 干预措施
Treatment (TLR8 agonist VTX-2337, PLD, and Paclitaxel)
Patients receive TLR8 agonist VTX-2337 SC on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 SC on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: TLR8 Agonist VTX-2337 (Drug)
Treatment (TLR8 agonist VTX-2337, PLD, and Paclitaxel)
Patients receive TLR8 agonist VTX-2337 SC on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 SC on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Treatment (TLR8 agonist VTX-2337, PLD, and Paclitaxel)
Patients receive TLR8 agonist VTX-2337 SC on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 SC on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (TLR8 agonist VTX-2337, PLD, and Paclitaxel)
Patients receive TLR8 agonist VTX-2337 SC on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 SC on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pegylated Liposomal Doxorubicin Hydrochloride (Drug)
Treatment (TLR8 agonist VTX-2337, PLD, and Paclitaxel)
Patients receive TLR8 agonist VTX-2337 SC on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 SC on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
First-cycle dose-limiting toxicities
时间窗: 28 days
Frequency and severity of toxicities as assessed by CTCAE
时间窗: Up to 1 year
次要结局
- Pharmacokinetic measures of TLR8 agonist VTX-2337(Baseline, 0.5, 2, 4, 8, and 24 hours after TLR8 agonist VTX-2337 injection)
- Pharmacokinetic measures of paclitaxel(Baseline, 0.5, 2, 4, 8, and 24 hours after TLR8 agonist VTX-2337 injection)
- Pharmacokinetic measures of pegylated liposomal doxorubicin hydrochloride(Baseline, 0.5, 2, 4, 8, and 24 hours after TLR8 agonist VTX-2337 injection)
- Immune activation (e.g., Th1, cytokines)(Up to 1 year)