A Phase 3, Randomized, Double-Blind Study of Pamrevlumab or Placebo in Combination With Either Gemcitabine Plus Nab-paclitaxel or FOLFIRINOX as Neoadjuvant Treatment in Patients With Locally Advanced, Unresectable Pancreatic Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- FibroGen
- 入组人数
- 284
- 试验地点
- 90
- 主要终点
- Overall Survival
研究概览
简要总结
This is a Phase 3, randomized, double-blind trial to evaluate the efficacy and safety of neoadjuvant treatment with pamrevlumab or placebo in combination with either gemcitabine plus nab-paclitaxel (G/NP) or FOLFIRINOX in the treatment of participants with locally advanced, unresectable pancreatic cancer.
详细描述
Participants will be randomized in a 1:1 ratio to one of the two study treatment arms; pamrevlumab with either G/NP or FOLFIRINOX, placebo with G/NP or FOLFIRINOX.
Each participant may receive up to 6 cycles of treatment (each treatment cycle is 28 days). Tumor tissue will be collected during resection to determine surgical outcome and for biomarker analysis. Tumor response will be evaluated by changes in CT scan, FDG-PET, CA 19-9, and NCCN® guidelines.
All participants randomized will have a safety follow-up visit approximately 28 days after the last dose of study treatment and a final safety follow-up phone call at approximately 60 days after the last dose.
Participants who complete study treatment will be evaluated for surgical exploration for possible R0 or R1 resection. Surgery will occur at least 4 weeks after the last dose (allowing for a wash-out period from treatment) and only after receipt of the recommendation from the central review board with regards to surgical eligibility. Surgery will occur no longer than 8 weeks after the last dose. Participants who undergo surgery will be evaluated for surgical complications for at least an additional 90 days following discharge from surgery.
Participants who are ineligible for surgical exploration (i.e. participants who did not complete study treatment or do not meet any of the protocol defined criteria or had a contraindication to surgery) will continue in the Follow-up period and receive treatment as per standard of care (SOC) for each institution.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Understand and sign informed consent; be willing to comply with study procedures, including surgery
- •Age ≥ 18 years
- •Be a male, or non-pregnant and non-lactating female
- •Negative serum B-hCG pregnancy test at screening for women of childbearing potential
- •Male participants with partners of childbearing potential and female participants of childbearing potential are required to use highly effective contraception methods during the conduct of the study and for 6 months after the last dose of study drug
- •Histologically or cytologically proven diagnosis of pancreatic ductal adenocarcinoma (PDAC)
- •Locally advanced pancreatic cancer considered unresectable according to NCCN Guidelines® Version 2.2018 as determined by central imaging
- •Measurable disease as defined by RECIST 1.1 criteria as determined by central imaging
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN), alkaline phosphatase <2.5 x ULN, and bilirubin ≤1.5 x ULN or in participants with biliary stenting ≤2.0 x ULN
- •Adequate bone marrow function: platelets >100,000 cells/mm3, hemoglobin >9.0 g/dl and absolute neutrophil count (ANC) >1,500 cells/mm3
- •Adequate renal function: creatinine < 1.5 x ULN, creatinine clearance ≥ 30 mL/min
- •Less than grade 2 pre-existing peripheral neuropathy (per CTCAE)
排除标准
- •Prior chemotherapy or radiation for pancreatic cancer
- •Previous (within the past 3 years) or concurrent malignancy diagnosis except non-melanoma skin cancer and in situ carcinomas (excluding in situ breast cancer)
- •Major surgery within 4 weeks prior to signing informed consent form. Biliary stents are permitted.
- •History of allergy or hypersensitivity to human, humanized or chimeric monoclonal antibodies
- •History of allergy or hypersensitivity to any of the chemotherapy agents being prescribed or their excipients
- •Any medical or surgical condition that may place the participant at increased risk while on study
- •Any condition potentially decreasing compliance to study procedures
- •Exposure to another investigational drug within 28 days of first dosing visit, or 5 half-lives of the investigational drug (whichever is longer)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infections, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Documented history of drug or alcohol abuse within 6 months of signing informed consent
- •Any medical condition that, in the opinion of the investigator, may pose a safety risk to a participant in this trial, may confound the assessment of safety and efficacy, or may interfere with study participation
- •Participants with a history of interstitial pulmonary disease, hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection
- •Participants who have been administered a live vaccine within 4 weeks prior to the first administration of therapy
- •Participants who cannot stop chronic medications that inhibit or induce cytochrome P (CYP) 2C8 or CYP3A4
- •Participants with poorly controlled comorbid conditions, including; congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), uncontrolled diabetes mellitus (DM) or neurologic disorders (not acutely related to pancreatic cancer) or limited function
研究组 & 干预措施
Arm A
Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX
干预措施: Pamrevlumab + Gemcitabine + Nab-paclitaxel or Pamrevlumab + FOLFIRINOX (Drug)
Arm B
Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX
干预措施: Placebo + Gemcitabine + Nab-paclitaxel or Placebo + FOLFIRINOX (Drug)
结局指标
主要结局
Overall Survival
时间窗: Up to approximately 5 years
Overall survival was defined as the time from date of randomization to date of death due to any cause. Overall survival was calculated using the Kaplan-Meier method.
次要结局
- Event-free Survival (EFS)(Up to approximately 5 years)
- Progression-free Survival (PFS) as Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1(Up to approximately 5 years)
- Number of Participants With Best Overall Objective Response as Assessed Using RECIST v1.1(Up to approximately 5 years)