Phase 1b & 2 Study With Olvi-Vec Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer (VIRO-15)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Number of Participants With Related Treatment-emergent Adverse Event [Safety and Tolerability] (Phase 1b)
研究概览
简要总结
The purpose of this study is to determine if Olvi-Vec oncolytic immunotherapy is well tolerated with anti-tumor activity in patients diagnosed with recurrent or refractory ovarian cancer and peritoneal carcinomatosis.
详细描述
Ovarian cancer (OC) remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemo-resistance and remarkable heterogeneity. There is an unmet medical need to develop new therapy modalities. In preclinical studies, Olvi-Vec, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 30 different human tumors, including ovarian cancer. Olvi-Vec has been investigated in early stage clinical trials in the United States and Europe via systemic delivery as monotherapy and in combination with other therapies, and via regional delivery as monotherapy. Olvi-Vec treatment was well tolerated across different malignancies, routes of administration, and monotherapy as well as combination therapy protocols. The ability of Olvi-Vec to infect tumor tissue and kill tumor cells was demonstrated. In addition, virus-induced immune activation and favorable anti-tumor immune response have been observed. Evidences of anti-tumor efficacy and clinical benefits have also been documented.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed, written informed consent.
- •High-grade serous (including Malignant Mixed Mullerian Tumor (MMMT) with metastasis that contains high grade epithelial carcinoma), endometrioid, or clear-cell ovarian cancer which includes: (1) platinum-resistant (recurrence or progression in < 6 months) or (2) platinum-refractory (progression while on platinum-based therapy); patient must have failed either at least 2 consecutive therapies or are not eligible for additional cytotoxic therapies (exception is Phase 2 receiving chemotherapy with/without bevacizumab).
- •Intermediate platinum-sensitive patients (recurrence of disease 6 to 12 months from last platinum compound treatment): Recurrent ovarian carcinoma with at least four prior individual treatment regimens including at least two separate platinum-based therapies with recurrence from the last platinum-based regimen less than 12 months, who are unwilling or unable to undergo additional platinum-based cytotoxic therapy (this sub-population is not applicable for Phase 2 receiving chemotherapy with/without bevacizumab).
- •Performance status ECOG is at 0 or 1, and life expectancy of 6 months
- •Has either measurable disease in the peritoneal cavity as defined by RECIST 1.1 (Phase 1b & 2) or has non-measurable disease in the peritoneal cavity (Phase 1b) and can be confirmed by laparoscopy and/or elevated CA-
- •Patients who have non-measurable disease that is not identifiable by PET/PET-CT scan, but who have elevated CA-125, and/or ascites, with visible disease confirmed by laparoscopy are also eligible.
- •Able to undergo IP injection.
- •Adequate renal, hepatic, bone marrow and immune functions.
- •Baseline tumor biopsy is required.
- •Documented progressive disease status at baseline (Phase 2).
排除标准
- •Tumors of mucinous subtypes, or non-epithelial ovarian cancers (e.g., Brenner tumors, Sex-cord tumors).
- •Unresolved bowel obstruction.
- •Known central nervous system (CNS) metastasis.
- •Known seropositivity for HIV or active hepatitis infection.
- •History of thromboembolic event within the last 3 months.
- •Pregnant or breast-feeding women.
- •Smallpox vaccination within 1 year of study treatment.
- •Clinically significant cardiac disease.
- •Received prior gene therapy or therapy with cytolytic virus of any type.
- •Receiving concurrent antiviral agent active against vaccinia virus.
- •Have known allergy to ovalbumin or other egg products.
- •Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or unhealed skin wounds or ulcers) as assessed by the Investigator.
- •Symptomatic malignant ascites and non-manageable pleural effusion.
- •Known hypersensitivity to bevacizumab, uncontrolled hypertension, history of stroke, or clinical findings suggestive of excessive risk for GL perforation (uncontrolled peptic ulcer disease, partial small bowel obstruction, etc.) that would make risks of bevacizumab unacceptable in the opinion of the investigator.
研究组 & 干预措施
Phase 2
Participants treated in the Phase 2 portion received 2 IP infusions of Olvi-Vec at 3 x 10e9 pfu followed by platinum-doublet chemotherapy with or without bevacizumab.
干预措施: Platinum-doublet with or without bevacizumab (Drug)
Phase 1b - Cohort 1
Participants treated in Cohort 1 received 2 IP infusions at 3 x 10e9 pfu.
干预措施: Olvi-Vec (Biological)
Phase 1b - Cohort 3
Participants treated in Cohort 3 received 2 IP infusions at 2.5 x 10e10 pfu.
干预措施: Olvi-Vec (Biological)
Phase 1b - Cohort 2
Participants treated in Cohort 2 received 2 IP infusions at 1 x 10e10 pfu.
干预措施: Olvi-Vec (Biological)
Phase 2
Participants treated in the Phase 2 portion received 2 IP infusions of Olvi-Vec at 3 x 10e9 pfu followed by platinum-doublet chemotherapy with or without bevacizumab.
干预措施: Olvi-Vec (Biological)
结局指标
主要结局
Number of Participants With Related Treatment-emergent Adverse Event [Safety and Tolerability] (Phase 1b)
时间窗: Change from baseline during Treatment and for 30 days following last dose over average of 2 years.
Determine safety and tolerability of administering 2 consecutive doses of Olvi-Vec via intraperitoneal catheter by the evaluation of the number of participants with related treatment-emergent adverse events (type, frequency, and severity) as assessed by CTCAE 4.03.
Progression-free Survival Following Treatment in Participants Enrolled in the Phase 2 Portion of Study With Platinum-resistant or Platinum-refractory Ovarian Cancer.
时间窗: For participants enrolled in the Phase 2 portion, outcome is from the date of starting chemotherapy until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Overall Response Rate (ORR) by Tumor Marker Cancer Antigen-125 (CA-125) for Participants Enrolled in the Phase 2 Portion of Study With Platinum-resistant or Platinum-refractory Ovarian Cancer
时间窗: Assessed pre-treatment, during treatment at 2- to 3-week intervals and post-treatment assessed up to 24 months.
To assess anti-tumor response by Overall Response Rate by Tumor Marker Cancer Antigen-125 (CA-125) for participants who were enrolled in the Phase 2 portion of this study with platinum-resistant or platinum-refractory ovarian cancer.
Overall Response Rate (ORR) by RECIST 1.1 for Participants Enrolled in the Phase 2 Portion of the Study With Platinum-resistant or Platinum-refractory Ovarian Cancer
时间窗: For evaluable participants enrolled in the Phase 2 portion of this study with platinum-resistant or platinum-refractory ovarian cancer who were assessed at pre-treatment, during treatment at 6- to 12-week intervals and post-treatment up to 24 months.
To assess anti-tumor response by Overall Response Rate (ORR) defined as disease control rate (DCR = CR + PR + SD≥15 weeks) by RECIST 1.1 criteria: Complete Response (CR) is a disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions; stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to quality for progressive disease; Progressive Disease (PD) is at least a 20% increase in sum of longest diameter of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions.
次要结局
- Clinical Benefit Rate(Approximately 24 months)
- Evaluation of Tumor Response to Treatment for Participants Enrolled in the Phase 1b Portion of This Study(Assessed post-treatment at 6 to 12 week intervals or until disease progression or death from any cause, whichever comes first, assessed up to 24 months.)
- CA-125 Response in Participants Enrolled in the Phase 1b Portion of This Study(Assessed pre-treatment, during treatment and post-treatment at 6 to 12 week intervals, assessed up to 24 months.)
- Determine Progression-free Survival Following Treatment (Phase 1b)(From the date of starting chemotherapy until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.)
- Overall Survival(By medical chart review until death or 3 years from the date of last treatment whichever comes first.)