NCT02580058已完成3 期
A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY OF AVELUMAB (MSB0010718C) ALONE OR IN COMBINATION WITH PEGYLATED LIPOSOMAL DOXORUBICIN VERSUS PEGYLATED LIPOSOMAL DOXORUBICIN ALONE IN PATIENTS WITH PLATINUM-RESISTANT/REFRACTORY OVARIAN CANCER
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 566
- 试验地点
- 256
- 主要终点
- Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
研究概览
简要总结
A Phase 3 global study comparing avelumab alone to avelumab plus PLD and to PLD alone to demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Overall Survival in patients with platinum resistant/platinum refractory ovarian cancer.
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 epithelial ovarian, fallopian tube, or peritoneal cancer, including malignant mixed Müllerian tumors with high grade serous component.
- •Platinum resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum based therapy (refractory), respectively.
- •Received up to 3 lines of systemic anticancer therapy for platinum sensitive disease, most recently platinum containing, and no prior systemic therapy for platinum resistant disease
- •Measurable disease by investigator assessment with at least 1 unidimensional measurable lesion by RECIST v.1.1 that has not previously been irradiated
- •Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- •Mandatory tumor biopsy must be performed prior to enrollment for all patients (unless there is a documented clinical contraindication). In addition, availability of archived FFPE tumor tissue should be confirmed. If a patient underwent tumor tissue collection within 3 months prior to enrollment with no intervening treatment, and the sample is provided, then a new de novo tumor biopsy is not required.
排除标准
- •Non epithelial tumor or ovarian tumors with low malignant potential (ie, borderline tumors).
- •Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways).
- •Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry and are neurologically stable.
- •Diagnosis of any other malignancy within 5 years prior to registration, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.
- •Severe gastrointestinal conditions such as clinical or radiological evidence of bowel obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of inflammatory bowel disease.
研究组 & 干预措施
avelumab
Experimental
Arm A: avelumab alone
干预措施: avelumab (Biological)
avelumab plus pegylated liposomal doxorubicin (PLD)
Experimental
Arm B: avelumab plus PLD
干预措施: avelumab (Biological)
avelumab plus pegylated liposomal doxorubicin (PLD)
Experimental
Arm B: avelumab plus PLD
干预措施: PLD (Drug)
PLD
Active Comparator
Arm C: PLD alone
干预措施: PLD (Drug)
结局指标
主要结局
Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
时间窗: From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.
PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.
Overall Survival (OS)
时间窗: From randomization until the date of first documented progression or date of deaths from any cause, whichever came first, assessed up to 30 months (based on cutoff date: 19 September 2018).
OS is defined as the time from the date of randomization to the date of death due to any cause. OS time was summarized by treatment arm using the Kaplan-Meier method.
次要结局
- Objective Response Rate (ORR) Based on BICR Assessment(Tumor assessments as assessed by BICR were conducted at every 8 weeks from screening until documented disease progression (approximately up to 30 months); based on cutoff date: 19 September 2018.)
- PFS Based on Investigator Assessment According to RECIST Version 1.1(From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.)
- ORR Based on Investigator Assessment(Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.)
- Disease Control (DC) Rate Based on BICR Assessment(Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.)
- DC Rate Based on Investigator Assessment(Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.)
- Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28(From Day 1 of Cycle 1 to prior to end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From the time of the first dose of study treatment through a minimum of 30 days + last dose of study treatment, start day of new anti-cancer therapy -1 day (up to 70 months); based on cutoff date: 13 July 2022.)
- Number of Participants With Laboratory Abnormalities(From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.)
- Number of Participants With Electrocardiogram (ECG) Abnormalities(From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.)
- Serum Trough Concentration (Ctrough) For Avelumab Following Cycle 2 Day 1 Pegylated Liposomal Doxorubicin (PLD) Dose(At predose (0 H) on Cycle 2 Day 1)
- Area Under The Concentration Time Profile From Time Zero to 24 Hours (AUC24) For Doxorubicin Following Cycle 2 Day 1 PLD Dose(From 0 through 24 hours postdose)
- Area Under The Concentration Time Profile From Time Zero to 336 Hours (AUC336) For Doxorubicin Following Cycle 2 Day 1 PLD Dose(From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose)
- Area Under The Concentration Time Profile From Time Zero to The Last Quantifiable Concentration (AUClast) For Doxorubicin Following Cycle 2 Day 1 PLD Dose(From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose)
- Number of Participants With Treatment-Induced Neutralizing Antibody (nAb)(At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab)
- Duration of Response (DR) Based on BICR Assessment(Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.)
- Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From Baseline(Screening, Cycle 3 Day 1 (repeated every 2 cycles) to the end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.)
- Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OS(Biomarkers are measured only at screening.)
- Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OS(Biomarkers are measured only at screening.)
- Change From Baseline in EQ-VAS Score at End of Treatment(Baseline and end of treatment/withdrawal visit)
- DR Based on Investigator Assessment(Tumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.)
- Change From Baseline in Vital Signs - Blood Pressure(From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.)
- Change From Baseline in Vital Signs - Pulse Rate(From screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.)
- Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoL(Day 1 of Cycle 1, Day 1 of each subsequent cycle, end of treatment/withdrawal visit and the 30, 60 and 90 days safety follow up visits, based on cutoff date: 19 September 2018.)
- Serum Maximum Concentration (Cmax) For Avelumab Following Cycle 2 Day 1 PLD Dose(At postdose (end of infusion, 1H) on Cycle 2 Day 1)
- Cmax For Doxorubicin Following Cycle 2 Day 1 PLD Dose(From predose (0 H) of Cycle 2 Day 1 through 336 hours postdose)
- Number of Participants With Treatment-Boosted Anti-Drug Antibody (ADA)(At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab)
- Number of Participants With Treatment-Induced ADA(At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab)
研究者
研究点 (256)
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