PHASE II Study - EFFICACY AND SAFETY OF (PARPi )Polyadenosine Diphosphoribose [Poly Polymerisation inhibitorTO TREAT PANCREATIC CANCER
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) by using RECIST 1.1
研究概览
简要总结
This is an open label, single arm, phase II trial of Olaparib for (PDAC) pancreatic ductal adenocarcinoma patients with BRCAness (breast cancer gene). All study subjects will receive Olaparib in a dose of 300 mg p.o twice daily. Treatment will continue until progression, intolerable toxicity or as per patient preference.
Primary objective:
To determine the efficacy of Olaparib monotherapy in stage IV pancreatic ductal adenocarcinoma (PDAC)with (BRCAness) BRCA -Breast Cancer susceptibility gene.
详细描述
An open label, single arm, phase II trial of Olaparib for PDAC patients with BRCAness (BRCA-Breast Cancer susceptibility gene).
Patients with previously identified Loss of ATM (ATM serine/threonine kinase)by (IHC) Immunohistochemistry OR (overall survival) - Family history of BRCA (Brest Cancer gene)-associated cancers: breast, ovarian, pancreatic, gastric or prostate must be present in 2 or more first-degree relatives OR- Patients with previously identified genetic aberrations that are associated with (HRD) Homologous recombination deficiency will be eligible [e.g. somatic BRCA mutation, Fanconi Anemia gene or RAD51(eukaryote gene) mutations].
All patients will be retrospectively investigated for (HRD)Homologous recombination repair deficiencies signature using transcriptome profiling and ATM expression and the results correlated with (PARPi) (Polyadenosine 5'diphosphoribose [poly (ADP ribose)] polymerization INHIBITOR) response rates.
Eligible patients will receive treatment with Olaparib tablets p.o 300 (mg) milligram twice daily until progression. Each treatment cycle is described as 28 days long. Patients will have tumor assessments according to RECIST 1.1(Response Evaluation Criteria In Solid Tumors) at baseline. Patients will then be followed for the final analysis of (OS) overall survival.
Eligible patients will be those patients with stage IV pancreas cancer previously treated for metastatic disease. Patients must have received one prior therapy for the treatment of metastatic disease or refused chemotherapy.
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
- All
- 接受健康志愿者
- 否
入选标准
- •• Patients must be male or female ≥18 years of age
- •Patients with histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas.
- •Patients must have tested negative for BRCA 1 or 2 germline deleterious mutation or be ineligible for BRCA testing [as determined by their insurer]
- •Patients with previously identified Loss of ATM by IHC OR
- •Family history of BRCA-associated cancers: breast, ovarian, pancreatic, gastric or prostate must be present in 2 or more first-degree relatives OR
- •Patients with previously identified genetic aberrations that are associated with HRD will be eligible [e.g. somatic BRCA mutation, Fanconi Anemia gene or RAD51 mutations].
- •Patients must have received at least one prior therapy for metastatic disease or have refused chemotherapy to be eligible
- •Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study. RECIST 1.1 has been modified to allow the assessment of progression due to new lesions in patients with no evidence of disease at baseline
- •(ECOG) Eastern Cooperative Oncology Group: A performance status using scales and criteria to assess how a patient's disease is progressing)Performance Status 0-1 (Karnofsky >70).
- •Patients must have adequate organ and marrow function as defined below:
- •Leukocytes >3,000 cells/mm3
- •Absolute neutrophil count >1,500 cells/mm3
- •Platelets >100,000 cells/mm3
- •Hemoglobin >9 g/dl (no blood transfusions within 4 weeks prior to enrolment)
- •Total bilirubin <1.5 X institutional upper limit of normal (IULN)
- •(AST) aspartate aminotransferase (SGOT)/(ALT) Alanine transaminase(SGPT) <2.5 X IULN without liver metastasis <5 X IULN for patients with liver metastasis
- •Creatinine within normal institutional limits OR
- •Creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- •(INR)international normalized ratio <1.5
- •Women of childbearing potential (defined as not post-menopausal for 12 months or no previous surgical sterilization) and fertile men must agree to use adequate contraception for the duration of study participation. Male subjects must agree to refrain from sperm donation during the study and for 30 days after the last dose of study drugs.
- •Ability to understand and the willingness to sign a written informed consent document. Signed informed consent form must be obtained prior to initiation of study evaluations and/or activities.
排除标准
- •Uncontrolled intercurrent illness including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia and myocardial infarction (MI) within 3 months of initiation of therapy.
- •Pregnancy or lactation
- •Patient has active and uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
- •Patient has undergone major surgical resection within 4 weeks prior to enrollment.
- •Patient received radiotherapy, surgery, chemotherapy, or an investigational therapy within 2 weeks prior to study entry.
- •Patient has serious medical risk factors involving any of the major organ systems such that the investigator considers it unsafe for the patient to receive an experimental research drug
- •Serious psychiatric or medical conditions that could interfere with treatment
- •History of prior malignancy unless the malignancy has been treated with no evidence of active disease and more than 2 years from initial diagnosis
- •Major bleeding in the last 4 weeks prior to study entry
研究组 & 干预措施
Single Arm
Only one Arm,All patients will receive Olaparib 300 (mg) milligram bid p.o till disease progression
干预措施: OLAPARIB (Drug)
结局指标
主要结局
Objective Response Rate (ORR) by using RECIST 1.1
时间窗: approximately- 24 months
Due to lack of results, study has been early terminated
次要结局
未报告次要终点