A Single-arm, Open-label, Phase 2 Study of JX-594 (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) Administered by 5 Weekly Intravenous (IV) Infusions in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Radiographic response of ovarian peritoneal carcinomatosis to JX-594 treatment
研究概览
简要总结
This is a single-arm open-label Phase 2 study in patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments. Patients will receive 5 weekly IV infusions of JX-594 until radiographically determined progressive disease. Patients will be allotted in a 1:1 ratio to undergo a laparoscopy and tumor biopsy 10 days after dose 1 or 10 days after Dose 5. Patients will be monitored on study until evidence of progression or death or for 12 months post treatment.
详细描述
This is a single-arm open-label Phase 2 study in patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments. Patients will receive 5 weekly IV infusions of JX-594 and will continue to receive IV infusion of JX-594 every 3 weeks until radiographically determined progressive disease. Using a 2 stage trial design, if 2 or more of the first 15 patients show a clinical response as defined by Response Evaluation Criteria in Solid Tumors 1.10 criteria (or if 3 of the 15 have stable disease as defined by Modified Response Evaluation Criteria in Solid Tumors 1.1 or clinically), the arm will be expanded to a total of 25 patients (Stage 2).
In Stage 1, patients will be allotted in a 1:1 ratio to undergo a laparoscopy and tumor biopsy 10 days after dose 1 or 10 days after Dose 5. A decision as to whether laparoscopy will be performed in Stage 2 will be reached at the conclusion of Stage 1.
Patients will be monitored on study until evidence of progression or death or for 12 months post treatment
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
- •Histologically confirmed ovarian carcinomatosis with; no curative treatment options available, or the patient has refused or cannot tolerate the standard therapy. Patients must have had prior primary platinum based chemotherapy.
- •Radiologically evaluable disease.
- •At least 2 tumor masses amenable to biopsy (excisional or core) or laparoscopy. Tumor masses selected cannot be followed by Response Evaluation Criteria in Solid Tumors 1.
- •Expected survival ≥12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Women aged ≥18 years
- •Sexually active patients must be able and willing to abstain for a minimum of 15 days after treatment with JX-594 and subsequently use barrier method for at least 6 weeks after the last JX-594 treatment
- •Signed informed consent form
- •No contraindications to undergo general anesthetic or laparoscopy.
- •Laboratory requirements:
- •Absolute neutrophil count (ANC) ≥1.0 x 109/L
- •Lymphocytes ≥0.5 x109/L
- •Hemoglobin ≥90 g/L (correction with transfusion or erythropoietin based therapy allowed)
- •Platelet count ≥75 x 109/L
- •Biochemistry
- •Total bilirubin ≤1.5 x upper limit of normal (ULN)
- •Alkaline Phosphatase (ALP), Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤3 x ULN (if patient exhibits liver metastasis, up to 5 x ULN acceptable)
- •Serum creatinine ≤1.5 x ULN or creatinine clearance is ≥1.0 mL/s according to Cockroft-Gault formula
- •International normalized ratio (INR) ≤1.5 Serum chemistries within normal limits (WNL) or Grade 1 (with exception of sodium, potassium, glucose, calcium, phosphate,magnesium, chloride upon Investigator discretion)
排除标准
- •Significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS) and/or medication (e.g., systemic corticosteroids taken for more than 4 weeks within the preceding 3 months). Intermittent doses of corticosteroids as an antiemetic for chemotherapy are acceptable. Patients have to be off continuous steroids for at least 4 weeks
- •Therapeutic anticoagulant therapy
- •History of severe exfoliative skin condition (e.g., eczema or ectopic dermatitis requiring systemic therapy for more than 4 weeks)
- •Tumor(s) invading a major vascular structure (e.g., carotid artery)
- •Clinically significant and uncontrolled pericardial or pleural effusions
- •Severe or unstable cardiac disease, including significant coronary artery disease (e.g., requiring angioplasty or stenting) within the preceding 12 months, unless well-controlled and on stable medical therapy for at least 3 months
- •Tumor burden >50% of abdominal cavity or malignant obstruction of small bowel or other condition that would preclude safe biopsy or laparoscopy
- •Brain metastasis: Viable central nervous system (CNS) malignancy associated with clinical symptoms (Note: enrollment allowed if completely resected or stable post radiotherapy >12 weeks).
- •Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
- •Prior participation in other research protocol involving an investigational product within 4 weeks or 5 half-lives, whichever is longer, prior to first treatment
- •Medical condition, laboratory abnormality or active infection that in the judgment of the Principal Investigator may increase the risk associated with study participation or may prevent laparoscopy or may interfere with interpretation of study results and/or otherwise make the patient inappropriate for study entry
- •Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX-594 dose. (Note: please consult Ozmosis Research Inc. if patient is taking any other anti-viral medications to determine eligibility)
- •Unable to receive IV contrast for CT scanning due to documented history of iodinated contrast allergy unless controlled by medical intervention (e.g., premedication with steroids, diphenhydramine, or other anti-allergic medications)
- •Pregnant or nursing an infant
- •Pulse oximetry O2 saturation <90% at rest on room air
- •Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination.
结局指标
主要结局
Radiographic response of ovarian peritoneal carcinomatosis to JX-594 treatment
时间窗: 6 weeks
Determine radiographic response rate (response evaluation criteria in solid tumors \[modified Response Evaluation Criteria in Solid Tumors 1.1\])to JX-595
次要结局
- Response of tumour markers to JX-594(Weekly)
- JX-594 Secondary Replication in blood over time(Weekly)
- Response rate using modified immune criteria(6 weeks)
- Delivery of JX-594 in solid tumours(Weekly)
- Immune response to JX-594(6 weeks)
- Assessment of Adverse Events related to JX-594 administered by repetitive IV infusion(Weekly)
- Time to progressive disease(6 weeks)
研究者
Andrea McCart
Gastrointestinal Surgical Oncologist
Mount Sinai Hospital, Canada