A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Physician's Choice of Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer (PRROC) (OnPrime, GOG-3076)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 186
- 试验地点
- 59
- 主要终点
- Progression-free survival (PFS) by RECIST 1.1 in the Intention-to-Treat (ITT) population (all randomized participants regardless of whether they received any dose of treatment)
研究概览
简要总结
The OnPrime study is a multi-center, randomized open-label phase 3 study evaluating the safety and efficacy of Olvi-Vec followed by platinum-doublet chemotherapy and bevacizumab compared to the Active Comparator Arm with Physician's Choice of chemotherapy and bevacizumab in women diagnosed with platinum-resistant/refractory ovarian cancer (includes fallopian tube cancer and primary peritoneal cancer). This Phase III trial builds on the efficacy and safety data reported in the previous Phase II VIRO-15 trial with promising objective response rate and progression-free survival observed in heavily pre-treated patients with platinum-resistant/refractory ovarian cancer. The phase II results also showed that the intra-peritoneal route of delivery was efficient in generating tumor cell killing and immune activation, and led to clinical reversal of platinum-resistance or refractoriness in this difficult-to-treat patient population.
详细描述
Olvi-Vec (olvimulogene nanivacirepvec, aka GL-ONC1, laboratory name: GLV-1h68) is an oncolytic vaccinia virus-based immunotherapy. This study is to test the hypothesis that the combination of Olvi-Vec followed by further chemotherapy is particularly effective against established tumors by virus-mediated immune activation and re-sensitization of tumor cells to chemotherapy. Participant population includes histologically confirmed non-resectable platinum-resistant/refractory ovarian cancer (PRROC). Determination of progression-free survival, safety and overall survival are key objectives. Participants randomized into the Experimental Arm will receive a single-cycle (2 infusions on two consecutive days) of Olvi-Vec through an intraperitoneal catheter. The catheter is then removed, and patients receive systemically administered platinum-doublet chemotherapy and bevacizumab. The control arm receives the Physician's Choice of chemotherapy and bevacizumab at the same dose and schedule. Biological samples will be obtained from some Experimental Arm participants for virus-shedding testing. Assessment of response to treatment in both arms will be by RECIST 1.1 and iRECIST as assessed by Blinded Independent Central Review. Maintenance/continued treatment with non-platinum chemotherapy and bevacizumab is dependent on a participant being clinically stable until confirmed progressive disease by iRECIST or can no longer tolerate therapy.
Dr. Robert W. Holloway (AdventHealth Cancer Institute, Orlando, FL) will serve as the National Principal Investigator for this Phase 3 study in PRROC.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed (from prior treatment) non-resectable ovarian, fallopian tube or primary peritoneal cancer.
- •High-grade serous [including malignant mixed Mullerian tumor (MMMT) with metastasis that contains high-grade epithelial carcinoma, FIGO grades 2 & 3 allowed], endometrioid, or clear-cell ovarian cancer.
- •Performance status ECOG of 0 or
- •Life expectancy of at least 6 months.
- •Received a minimum of 3 prior lines (including the 1st line) of systemic therapy with no maximal limit.
- •Platinum-resistant or -refractory disease based on platinum-free interval (PFI) from the last dose of the most recent. platinum-based line of therapy (must have received a minimum of 2 doses of platinum in that line) to subsequent disease progression based on radiological assessment. Platinum-refractory: PFI of < 1 month (including disease progression while on platinum-based therapy). Platinum-resistant: PFI of 1-6 months.
- •Received prior bevacizumab (or biosimilar) treatment.
- •No contraindication to receive carboplatin, cisplatin or bevacizumab (or biosimilar).
- •Have disease progression after last prior line of therapy based on radiological assessment prior to randomization.
- •At least 1 measurable target lesion per RECIST 1.1 based on abdominal/pelvis imaging scan at screening.
- •Evidence by CT and/or PET scans or physical exam of abdominal/pelvis region likely having disease in the peritoneal cavity (i.e., peritoneal carcinomatosis).
- •Adequate renal, hepatic, bone marrow function, adequate coagulation tests, adequate immune function by lymphocyte count.
排除标准
- •Tumors of mucinous, low-grade serous, squamous cell, small cell neuroendocrine subtypes, MMMT tumors absent an epithelial component on recent biopsy, or non-epithelial ovarian cancers (e.g., germ cell tumors, Sex-cord tumors).
- •Bowel obstruction within last 3 months prior to screening.
- •Active urinary tract infection, pneumonia, other systemic infections.
- •Active gastrointestinal bleeding.
- •Known current central nervous system (CNS) metastasis.
- •Inflammatory diseases of the bowel.
- •History of HIV infection.
- •Active hepatitis B virus or hepatitis C virus within 4 weeks prior to study.
- •History of thromboembolic event within the prior 3 months.
- •Contraindications for intraperitoneal (IP) catheter placement: Bowel obstruction with distended abdomen, rigid abdomen with bulky anterior wall carcinomatosis, abdominal wall hernia mesh that precludes laparoscopic entry to abdomen.
- •Clinically significant cardiac disease at screening (New York Heart Association Class III/IV).
- •Acute cerebrovascular event(s) such as cerebrovascular accident (CVA) or transient ischemic attack (TIA) in previous 6 months.
- •Oxygen saturation <90%.
- •Received prior virus-based gene therapy or therapy with cytolytic virus of any type.
- •Receiving concurrent antiviral agent.
- •Prior malignancy of other histology active within previous 3 years except for locally curable cancers apparently cured such as basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast, any other stage I/II local malignancies.
- •Received chemotherapy, radiotherapy, other anti-cancer biologic therapies within 4 weeks prior to planned treatment.
- •Underwent surgery within 4 weeks, or have insufficient recovery from surgical-related trauma or wound healing, prior to first study treatment in either Arm.
- •Receiving immunosuppressive therapy or steroids (except acute concurrent corticosteroid of no more than 20 mg per day for medical management with prednisolone equivalent.
- •Symptomatic malignant ascites or pleural effusions defined as rapidly progressive ascites with abdominal distension and gastrointestinal dysfunction, pleural effusions with respiratory difficulties requiring frequent paracentesis > once every 14 days.
- •Known hypersensitivity to gentamicin.
研究组 & 干预措施
Olvi-Vec + Platinum-doublet & bevacizumab
Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0
Platinum-doublet & bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5
干预措施: olvimulogene nanivacirepvec (Biological)
Physician's Choice of Chemotherapy & bevacizumab
Physician's Choice of chemotherapy & bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).
干预措施: Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin (Drug)
Olvi-Vec + Platinum-doublet & bevacizumab
Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0
Platinum-doublet & bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5
干预措施: Bevacizumab (or biosimilar) (Drug)
Physician's Choice of Chemotherapy & bevacizumab
Physician's Choice of chemotherapy & bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).
干预措施: Bevacizumab (or biosimilar) (Drug)
Physician's Choice of Chemotherapy & bevacizumab
Physician's Choice of chemotherapy & bevacizumab (or biosimilar) administered beginning in Week 0. Physician's Choice of chemotherapy includes either a single agent non-platinum chemotherapy, or as platinum chemotherapy is allowed as an option, a platinum-doublet (i.e., platinum agent combined with a non-platinum agent).
干预措施: Platinum chemotherapy: carboplatin (preferred) or cisplatin (Drug)
Olvi-Vec + Platinum-doublet & bevacizumab
Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0
Platinum-doublet & bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5
干预措施: Platinum chemotherapy: carboplatin (preferred) or cisplatin (Drug)
Olvi-Vec + Platinum-doublet & bevacizumab
Olvi-Vec: A total of 2 consecutive days of intraperitoneal catheter infusions in Week 0
Platinum-doublet & bevacizumab (or biosimilar) administered beginning in Week 4 (preferred), but no later than Week 5
干预措施: Non-platinum chemotherapy: Physician's Choice of gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin (Drug)
结局指标
主要结局
Progression-free survival (PFS) by RECIST 1.1 in the Intention-to-Treat (ITT) population (all randomized participants regardless of whether they received any dose of treatment)
时间窗: From date of randomization up to 12 months
To assess progression-free survival from time of randomization until first documented disease progression based on radiological assessment or death from any cause.
次要结局
- Incidence of Treatment-emergent Adverse Events in the ITT population(From date of first study treatment until death or study completion; assessed up to 36 months)
- PFS by RECIST 1.1 in the modified ITT (mITT) population (participants who received at least 1 dose of treatment in either Arm)(From date of randomization up to 12 months)
- PFS by iRECIST in the ITT population(From date of randomization up to 12 months)
- Duration of Response (DOR) by RECIST 1.1 in the ITT population(From date of randomization up to 12 months)
- Overall Response Rate (ORR) by RECIST 1.1 in the ITT population(From date of randomization up to 12 months)
- Overall Survival in the ITT population(From date of randomization until death or study completion; assessed up to 36 months)