A Randomized Phase II Trial Comparing Molecularly Tailored Therapy to Physician's Discretion Standard of Care as Second-Line Therapy for Patients With Metastatic Pancreatic Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- 4 month progression free survival rate
研究概览
简要总结
The purpose of this study is to determine whether molecularly tailored therapy can improve the efficacy of treatment when compared to standard chemotherapy combinations for patients with metastatic pancreatic cancer receiving their second line of therapy for metastatic disease.
详细描述
This is an open label, randomized Phase II trial for patients with metastatic pancreatic cancer. The trial is designed to compare the outcomes (primary endpoint will be progression-free survival (PFS)) for patients who receive molecularly-tailored therapy (MTT) to those who receive physician discretion standard of care (SOC). To successfully allow for this assessment, and minimize confounding variables, we will need to ensure that:
- There is enough tissue for the molecular profiling to occur. Thus, only patients with adequate tumor tissue will be allowed to enroll.
- There is enough time for the molecular profiling to be completed; for the medical review panel (MRP) to render a determination on the optimal molecularly-guided therapy; and for the treating physician to obtain access to therapies, particularly if the MRP-determined therapy includes an off-label treatment OR a clinical trial. We anticipate this process will take a minimum of 4 weeks.
These factors will inevitably lead to a selection bias towards patients with a better prognosis. However, the randomization design should mitigate this selection bias.
Patients with metastatic pancreatic cancer who are actively on (or about to initiate) first-line therapy, who meet the inclusion and exclusion criteria as detailed in Section 3 will be enrolled. For all enrolled patients, at the time of enrollment, the treating physician will be asked to submit the planned second line SOC treatment he/she would recommend.
In an effort to streamline accrual, and based on data that demonstrate that the tumor genetic profile does not change significantly overtime in patients with pancreatic cancer, archived tumor tissue may be used for determination of MTT. The archived tissue may be, for example, core needle biopsies obtained at the time of establishing the diagnosis of metastatic disease; or for example, a surgical specimen obtained prior to the identification of metastatic disease. Archived tissue may be used as long as there is sufficient tissue for full molecular testing. Of note, even if sufficient archived tissue is available for testing, patients will still be required to undergo a new biopsy to obtain fresh tissue for ex vivo analysis, prior to initiation of second line therapy.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic adenocarcinoma of the pancreas (at enrollment)
- •Actively on (or about to initiate) first line therapy for metastatic pancreatic cancer (at enrollment)
- •Patients may have had neo-adjuvant and/or chemotherapy that must have been completed >3 months prior to starting first line therapy
- •Patients may be actively on "maintenance" therapy, such as maintenance capecitabine up to starting first line therapy for metastatic disease
- •Radiographically measurable disease (prior to initiation of second-line therapy)
- •Tumor deposits that are clearly accessible for serial tumor biopsies - A patient's biopsied lesion must be at least 1cm in diameter (in at least one dimension) (prior to initiation of second-line therapy)
- •Age ≥ 18 years (at enrollment)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Table 6, Appendix D) (at enrollment)
- •Adequate hepatic, bone marrow, and renal function at the time of enrollment AND at initiation of second line therapy:
- •Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 75,000/mm3; Hemoglobin ≥ 9.0 g/dL
- •Patients may have a transfusion of red blood cells to meet the hemoglobin requirement
- •Renal function: Serum creatinine ≤ 1.5 X upper normal limit of institution's normal range OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal
- •Hepatic function: Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 X the upper normal limit of institution's normal range; bilirubin ≤ 1.5 X the upper limit of normal. For patients with known hepatic metastases, AST and ALT ≤ 5 X the upper normal limit of institution's normal range
- •Prothrombin Time and Partial Thromboplastin Time (PTT) must be ≤ 2 X the upper limit of the institution's normal range and International Normalized Ratio (INR) <
- •Subjects on anticoagulation (such as coumadin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator
- •Patients must have fully recovered from all effects of surgery (prior to initiation of second-line therapy). Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring "Twilight" sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator.
- •Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential (at enrollment).
- •Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures (at enrollment).
排除标准
- •Known or suspected brain or central nervous system metastases, irrespective of prior treatment
- •The subject has had another active malignancy within the past three years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Questions regarding the inclusion of individual subjects should be directed to the Study Chair.
- •Clinically significant peripheral neuropathy at the time of enrollment (defined in the NCI Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v4.0] as grade 2 or greater neurosensory or neuromotor toxicity)
- •Patients receiving any other investigational agents.
- •Active severe infection, or known chronic infection with HIV or hepatitis B virus
- •Patients with chronic Hepatitis C virus may be enrolled if there is no clinical/laboratory evidence of cirrhosis AND the patient's liver function tests fall within the parameters set in Section 3.2.7.3, Inclusion Criteria, Hepatic function
- •Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke within the last 3 months, or a diagnosis of congestive heart failure
- •Life-threatening visceral disease or other severe concurrent disease
- •Women who are pregnant or breastfeeding
- •Anticipated patient survival under 2 months
研究组 & 干预措施
Molecularly Tailored Therapy
Patients will be treated according to their molecular profile and accordingly, the 29 evaluable patients enrolled may receive one of a dozen, or dozens of treatment regimens.
干预措施: Molecularly Tailored Second Line Therapy (Other)
Physician's Discretion Standard of Care
Patients will be treated according to physician discretion standard of care regimen.
干预措施: Standard of Care Second Line Therapy (Drug)
结局指标
主要结局
4 month progression free survival rate
时间窗: 4 months after treatment start
4 month progression free survival rate (PFS4mos) of MTT vs. SOC therapy as second line therapy in patients with metastatic pancreatic cancer
次要结局
- Disease control rate(6 months)
- Median progression-free survival(60 months)
- Median overall survival(60 months)
- Objective Response Rate(60 months)
- Change in tumor marker levels(60 months)