A Phase I/Ib Pilot Trial, Single Arm, Open Label, of Protein-Bound Paclitaxel, Cisplatin, and Gemcitabine (GCN) Combined With Tumor Treatment Fields (TTF) in Patient With Metastatic Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Mayo Clinic
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Safety of (m)-GCN+TTF
研究概览
简要总结
This is a Phase I/Ib trial, single-center, non-randomized, open-label study of Protein-bound Paclitaxel, Cisplatin, And Gemcitabine (GCN) Combined with Tumor Treatment Fields (TTF) and G+TTF maintenance therapy in patients with metastatic pancreatic cancer.
详细描述
GCN is predicted to be the front-line therapy for biliary and pancreatic cancer in the future given excellent results of current early clinical trials (ORR ≥ 67% in pancreatic cancer). This will change standard of care for front-line therapy in patients with stage IV pancreatic cancer. In this cohort of patients' tolerability after 6 cycles of therapy will be a challenge. Investigators hypothesize that developing a maintenance strategy with TTF+G will be cutting edge approach and can potentially transform front-line standard of care therapy in patients with stage IV pancreatic cancer. If this pilot study proves fruitful then a larger study to confirm findings can be conducted.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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 or cytologically confirmed pancreatic adenocarcinoma or adenosquamous carcinoma with liver metastasis. Liver metastasis can be confirmed histologically / cytologically or radiologically
- •Subjects with additional sites of metastasis, except known brain metastasis, are eligible
- •Histologies excluded include squamous, small cell carcinoma, and acinar cell carcinoma. However, adeno-squamous and acinar-adenocarcinoma histologies can be enrolled
- •Patients who have recurrence or metastasis after surgery and adjuvant therapy do not need repeat biopsy for confirmation of recurrence if clinical suspicion is high per scans (magnetic resonance imaging [MRI]/computed tomography [CT] scan), with and without CA 19-9 elevation, specifically if biopsy is unsafe or technically difficult
- •Patients with no prior lines of therapy for the treatment of stage IV metastatic disease
- •Patients could have had prior neoadjuvant or adjuvant chemotherapy or chemoradiotherapy
- •Patients who received gemcitabine-based adjuvant chemotherapy can enroll if they progress > 6 months after completion of the therapy
- •Patients who progress while on adjuvant fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) can enroll immediately
- •Male and female patients at least 18 years of age
- •Absolute neutrophil count (ANC) > 1500 cells/mm^3
- •Platelet count > 100,000 cells/mm^3
- •Hemoglobin >= 8 g/dL
- •Total bilirubin < 1.5 X upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 X ULN
- •For patients with known liver metastases or liver neoplasms: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 6.0 X ULN and total bilirubin < 3 x ULN
- •Serum creatinine within normal limits (WNL) or creatinine clearance > 50 mL/min
- •QT intervals: corrected QT (QTc) =< 470 msec for men and =< 490 msec for women (as measured by Hodges' Equation)
- •Estimated life expectancy of at least 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Ability to operate the Novo TTF-100L (P) / Novo TTF-200T system
- •Patients must have measurable disease on scans per RECIST 1.1
- •Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days after the completion of study treatment
排除标准
- •Previous front-line therapy for metastatic disease
- •Patients with known brain metastasis
- •Cardiac conduction abnormalities such as 2nd and 3rd heart-block requiring a pacemaker
- •Patient with cardiac or abdominal pacemakers or stimulators
- •Significant risk of cardiac drug toxicity due to congestive heart failure or history of myocardial infarction
- •Any other condition including but not limited to major co-morbidities, which in the opinion of the investigator would render the patient ineligible
- •Concomitant use of drugs that have black box warning of Torsades de Pointes will also be prohibited if cannot be replaced by another drug
- •Known sensitivity to conductive hydrogels
- •Patients who are pregnant or breastfeeding
- •Patients who lack the capacity to consent for themselves
研究组 & 干预措施
Modified GCN+TTF treatment
The trial will compose of 2 parts with a total of 40 subjects. The regimen will consist of gemcitabine (G) administered at a dose of 800 mg/m2, cisplatin (C) 30 mg/m2, and protein-bound paclitaxel (N) 150 mg/m2 administered on cycle 1 day 1 and every 2 weeks thereafter and TTF will be administered daily (150kHz 18 hours/day) starting with Cycle 1 Day 1 (dose level 1). After completing 6 cycles, patients will then transition to a maintenance phase of G administered at a dose of 1000 mg/m2 every 2 weeks and daily TTF (150 KHZ 18 hours/day) until progression of disease (POD) per RECIST v1.1. If 6 patients tolerate the dose level of GCN+TTF through the 1st cycle without defined dose limiting toxicities (DLTs) or grade 4 treatment related adverse events (TRAE), the 2nd part of the study (phase Ib portion) will commence. An additional 34 patients will be enrolled in the expansion cohort (phase Ib).
干预措施: Modified GCN+TTF treatment (Combination Product)
结局指标
主要结局
Safety of (m)-GCN+TTF
时间窗: 28 days
Assessed by incidence of adverse events, as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
次要结局
- Time to Progression (TTP)(Twelve months)
- Quality of Life - EORTC QLQ-C30(Every 2 months, up to 12 months)
- Progression-free Survival (PFS)(Six months)
- Overall Response Rate (ORR)(Six months)
- Overall Survival (OS)(Twelve months)