Phase 1b/2, Single Arm Clinical Trial to Evaluate the Safety and Activity of Oregovomab and Bevacizumab, Paclitaxel Carboplatin as a Combinatorial Strategy in Subjects With BRCA-wild Type Platinum Sensitive Recurrent Ovarian Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 10
- 主要终点
- Safety and Tolerability
研究概览
简要总结
This is a single arm phase 1b/2 evaluation of the combination of oregovomab, and bevacizumab, paclitaxel carboplatin in adult subjects with CA125-associated, advanced recurrent epithelial ovarian, fallopian tube or peritoneal carcinoma (FIGO Stage III/IV) with BRCA-wild type, previously treated with 1 prior lines of therapy, and with platinum free intervals of >6 months since last platinum-based treatment.
详细描述
This study is an open-label, single arm, phase 1b/II, multicenter study.
In phase 1b part, the recommended phase 2 dose of oregovomab combined with bevacizumab, paclitaxel and carboplatin will be examined. Approximately 3 to 12 subjects("3+3" dose finding design) will be enrolled in phase 1b trial with starting dose of 2mg oregovmab.
In Phase II trial, response rate of combination with oregovomab and bevacizumab, paclitaxel will be examined. Based on Simon's two stage model, 8 patients will be enrolled in first stage, after review of efficacy (response rate) of study treatment, 30 additional subjects for second stage of phase 2 will be enrolled. Considering 10% of screening failure rate, overall 42 patients will be enrolled in phase 2 trial.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult females (19 years old and older) with CA125-associated recurrent epithelial adenocarcinoma of ovarian, fallopian tube or peritoneal origin.
- •Have one of the eligible histologic epithelial cell types: serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, carcinosarcoma, transitional cell carcinoma, malignant Brenner's Tumor, or adenocarcinoma not otherwise specified (N.O.S.).
- •Patients must have had a complete or partial response to front-line platinum-based therapy (at least three cycles) and a treatment -free interval without clinical evidence of progressive disease at least 6 months.
- •No known deleterious or pathogenic germline or somatic BRreast CAncer gene (BRCA) mutation
- •Must have had an elevated serum CA125 > 2 times of UNL measured at the first diagnosis or screening within 28 days of start of study treatment.
- •Must have measurable disease, including identification of marker lesions, by radiographic or physical criteria suitable for evaluation according to RECIST v1.1 for documentation of disease response or progression.
- •Must have a ECOG Performance Status of 0, 1 or 2
- •Must have adequate organ function defined as:
- •neutrophil count ≥1000 μL
- •platelet count ≥100,000 μL
- •Hemoglobin >9.0 g/dl
- •Serum creatinine <1.5 times the upper normal limits (UNL) or creatinine clearance > 45 mL/min/1.73 m2
- •bilirubin <1.5 times the UNL
- •SGOT and SGPT < 2 times the UL
- •Must have voluntarily agreed to participate and have signed the informed consent, and are willing to complete all study procedures.
排除标准
- •Patients who have received more than one line of chemotherapy (maintenance is not considered a second line)
- •Have an active autoimmune disease (e.g., rheumatoid arthritis, SLE, ulcerative colitis, Crohn's Disease, MS, ankylosing spondylitis) requiring continuing immune suppressive therapy
- •Use of immunosuppressants within 28 days prior to the first administration of the current or clinical trial drug. However, intranasal, inhalation, and systemic administration of prednisone 10 mg/day or a physiological dose not exceeding the equivalent dose of corticosteroids are recognized as exceptions.
- •Known allergy to murine proteins or have had a documented anaphylactic reaction to any drug, or a known hypersensitivity to diphenhydramine or other antihistamines of similar chemical structure.
- •Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections (testing during the study is not mandatory).
- •Recognized immunodeficiency condition including human immunodeficiency virus (HIV) infection, cellular immunodeficiencies, hypogamma globulinemia or dysgammaglobulinemia; subjects who have acquired, hereditary, or congenital immunodeficiency's, including HIV infection
- •Patients with previous solid organ transplantation
- •Evidence of clinically significant cardiovascular conditions including uncontrolled hypertension, myocardial infarction within 1 year, uncontrolled or unstable angina, congestive heart failure (New York Heart Association Class III or IV), arrhythmia (Grade 2 or higher), chronic obstructive pulmonary disease, clinical significant proteinuria (>1g/24hr urine)
- •Patients with other invasive malignancies, with the exception of non-melanomatous skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates with this protocol.
- •Have ever previously received oregovomab or bevacizumab
- •Patients who received major surgical procedure within 28days
- •Pregnant or breast-feeding
研究组 & 干预措施
oregovomab, bevacizumab, paclitaxel and carboplatin
Combination of anti-angiogenesis and Chemo-immunotherapy
干预措施: Oregovomab (Biological)
oregovomab, bevacizumab, paclitaxel and carboplatin
Combination of anti-angiogenesis and Chemo-immunotherapy
干预措施: Bevacizumab (Drug)
oregovomab, bevacizumab, paclitaxel and carboplatin
Combination of anti-angiogenesis and Chemo-immunotherapy
干预措施: Carboplatin (Drug)
oregovomab, bevacizumab, paclitaxel and carboplatin
Combination of anti-angiogenesis and Chemo-immunotherapy
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: 1cycle (21days)
Assessment of Dose Limiting toxicity (DLT) based on incidences and severity of adverse events will be measured according to CTCAE v5.0
Efficacy based on overall response rate (ORR)
时间窗: Every 6 weeks (each cycle is 21 days)
Overall response rate measured as the Percentage of Participants with a Complete Response (CR) or Partial Response (PR), as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECISTv1.1)
次要结局
- Overall Survival (OS)(Date of randomization up until date of death from any cause)
- Progression Free Survival (PFS)(Date of randomization up until date of first documented disease progression or date of death from any cause, whichever comes first)
研究者
Jung KH, MD
Professor
Korean Cancer Study Group