Cisplatin Based Regimen to Patients With Advanced Pancreatic Cancer and Homologous Recombination Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- progression-free survival, PFS
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of cisplatin based regimen to patients with advanced pancreatic cancer and homologous recombination deficiency.
详细描述
Pancreatic adenocarcinoma (PDAC) is a highly lethal malignancy with a 5-year survival less than 10%. Approximately 80% of patients with pancreatic cancer are diagnosed at an advanced stage. Chemotherapy is one of the major treatments for advanced pancreatic cancer. In 2011, the PRODIGE trial has shown that oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) was associated with a survival advantage but had increased toxicity.
Defects in DNA damage response (DDR) genes causing homologous recombination deficiency (HRD) identify a clinically relevant subgroup of patients with PDAC, with both therapeutic and preventative implications. Accumulating evidence from nonrandomized and randomized clinical trials suggests HRD as a putative biomarker of therapeutic response for platinum-based chemotherapy in patients with advanced PDAC. Within HRD, germline variants in BRCA1 and BRCA2 are associated with improved progression-free survival in patients with platinum-sensitive metastatic PDAC treated with the poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib as maintenance therapy. Interestingly, based on preclinical evidence and phase II nonrandomized clinical trials, additional non-BRCA HRD aberrations may predict sensitivity to PARPi with other therapeutic strategies targeting DDR currently under clinical investigation (including immunotherapy, ATM, ATR, and PALB2 inhibitors). However, the efficacy of cisplatin based regimen as a second line treatment for patients with HRD has not been systematically studied.
The purpose of this study is to evaluate the efficacy of cisplatin based regimen on improving the progression-free survival (PFS) of advanced pancreatic cancer patients who harbor germline or somatic homologous recombination deficiency. These patients are resistant to at least one line of systemic chemotherapy. PFS, objective response rate (ORR), overall survival (OS) and disease control rate (DCR) are measured every four weeks.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand and the willingness to sign a written informed consent document.
- •Age ≥ 18 years and ≤ 80 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Histologically or cytologically confirmed advanced pancreas adenocarcinoma.
- •Tumor progression after at least one line of chemotherapy.
- •Genetic or molecular test confirmed the presence of homologous recombination deficiency.
- •Presence of at least of one measurable lesion in agreement to RECIST criteria.
- •The expected survival ≥ 3 months.
- •Adequate organ performance based on laboratory blood tests.
- •Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
排除标准
- •Pregnant or nursing women.
- •Primary pancreatic cancer.
- •Patients who have received platinum or PARPi treatment.
- •The diagnosis was confirmed by pathology as non-adenocarcinoma of pancreas.
- •Inflammation of the digestive tract, including pancreatitis, cholecystitis, cholangitis, etc.
- •Severe and uncontrollable accompanying diseases that may affect protocol compliance or interfere with the interpretation of results.
- •Renal insufficiency or dialysis
- •Other serious accompanying illnesses, which, in the researcher's opinion, could seriously adversely affect the safety of the treatment.
- •Patients who are allergic to cisplatin or other platinum drugs.
- •Patients who are unwilling or unable to comply with study procedures.
研究组 & 干预措施
Cisplatin
Cisplatin 25 mg/m2, ivgtt, 30 min, D1, 8.
干预措施: Cisplatin (Drug)
结局指标
主要结局
progression-free survival, PFS
时间窗: At the end of Cycle 1 (each cycle is 21 days)
PFS of subjects from recruiting to the time of disease progression
次要结局
- objective response rate (ORR)(At the end of Cycle 1 (each cycle is 21 days))
- Overall survival，OS(At the end of Cycle 1 (each cycle is 21 days))
- disease control rate (DCR)(At the end of Cycle 1 (each cycle is 21 days))