Phase Ib-II, Non-randomized, Open-label Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant With modFOLFIRINOX for Front-line Treatment of Metastatic Pancreatic Adenocarcinoma (NOVOFFOX)
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Clinica Universidad de Navarra, Universidad de Navarra
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Toxicity profile in patients with mPDAC treated at 1L with TTFields concomitantly with modFOLFIRINOX
概览
简要总结
The purpose of this clinical trial is to assess the safety and tolerability of TTFields in combination with chemotherapy in adults with metastatic pancreatic adenocarcinoma based on treatment-emergent adverse events of chemotherapy (modFOLFIRINOX) or device (TTFields).
The main questions it aims to answer are:
- Is TTFields treatment safe for the patients in combination with modFOLFIRINOX?
- Are participants compliant with the treatment?
- Is Is TTFields treatment effective in combination with modFOLFIRINOX against metastatic pancreatic adenocarcinoma?
详细描述
This is a phase Ib-II, non-randomized, open-label, one arm, multi-center study of the combination of NovoTTF-200T system with modFOLFIRINOX for the evaluation of the safety of the treatment in patients with metastatic pancreatic adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is the eight cause of cancer mortality in men and ninth in women worldwide. Nearly 50,000 patients are diagnosed annually and almost all of them are expected to die from the disease without any challenges in survival in the last decade. Unfortunately, in most of the cases the disease is already disseminated when tumor related symptoms appear, with 5-year survival rate of less than 8 percent in this population (Siegel et al, 2020).
Tumor Treating Fields (TTFields) are a non-invasive regional antimitotic treatment with minimal toxicity. TTFields act by delivering alternate low-intensity electric fields (1-3 V/cm), intermediate frequency (100-300 kHz), and alternating electric fields to the tumor using non-invasive transducer arrays placed on the skin around the region of the body containing the tumor. TTFields act predominantly during two phases of mitosis: 1) during metaphase, by disrupting the formation of the mitotic spindle; and 2) during cytokinesis, by dielectrophoretic dislocation of intracellular constituents, leading apoptosis.
There is an increasing interest in the addition of immunotherapy to treatment pancreatic adenocarcinoma. Thus, combining TTFields with immunotherapy represents an interest for future clinical trials. However, the combination of TTFields with FOLFIRINOX chemotherapy scheme has not been evaluated yet. In this trial, it is proposed to evaluate the combination of TTFields with modFOLFIRINOX chemotherapy in metastatic PDAC patients with liver metastases. The aim is to analyze both the safety of combining TTFields with modFOLFIRINOX chemotherapy scheme, and to study the potential effect of TTFields and chemotherapy on the TME of liver metastasis.
Each patient shall participate in the trial for a maximum of 24 months. The trial will consist in two consecutive parts:
- A first part (Phase Ib) consisting of a safety run-in cohort: This first part will include 6 patients that will be treated with standard dose of modFOLFIRINOX scheme combined with TTFields.
- A second part (Phase II) consisting of an expansion cohort in which the rest of accorded patients will be included.
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
- •All the patients should comply with the following criteria for inclusion:
- •Histological/cytological diagnosis of pancreatic adenocarcinoma.
- •The patient should be 18 years of age and older.
- •The patient has given consent to participate in the study.
- •The patient should be able to comply with all the requirements of the clinical trial.
- •Life expectancy of at least 3 months.
- •Metastatic disease with, at least, one hepatic lesion that must be accessible for biopsy.
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumor v1.1 (RECIST 1.1) apart from the liver lesion to be biopsied.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Amenable and assigned by the investigator to receive therapy with modFOLFIRINOX.
排除标准
- •Patients who present any of the following criteria for exclusion cannot be included in the clinical trial:
- •Malignancies other than pancreatic cancer within 3 years prior to Cycle 1 Day 1 (C1D1) with the exceptions of those with a negligible risk of metastasis or death (e.g., expected 5-year overall survival higher than 90 percentage), treated with expected curative outcome (such as but not limited to: adequately treated in situ carcinoma of the cervix, basal squamous or melanomatous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ of the breast treated surgically with curative intent).
- •Previous treatment with chemotherapy for metastatic pancreatic ductal adenocarcinoma.
- •Untreated CNS metastases. Treatment of brain metastases, either by surgical or radiation techniques, must have been completed at least 4 weeks prior to study entry.
- •Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the patient for 5-fluorouracil (5-FU) toxicity.
- •Previous radiation therapy within 14 days prior to C1D1 and/or persistence of radiation-related adverse effects.
- •Implantable electronic medical devices in the torso, such as pacemakers.
- •Known severe hypersensitivities to medical adhesives or hydrogel, or history of severe allergic, anaphylactic, or other hypersensitivity reactions to any of the study treatments used.
- •Spinal cord compression not definitively treated with surgery and/or radiation.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
结局指标
主要结局
Toxicity profile in patients with mPDAC treated at 1L with TTFields concomitantly with modFOLFIRINOX
时间窗: From the beginning of the first treatment cycle (cycle 1; each treatment cycle is 14 days) through study completion (for a maximum of 24 months per patient since inclusion)
Toxicity profile measured by the rate of patients with treatment-emergent adverse events (TEAEs), using CTCAE v5.0
次要结局
- Total hours with TTField device functioning during every 14 days chemotherapy cycle(From the beginning of the first treatment cycle (cycle 1; each treatment cycle is 14 days) until discontinuation of last study treatment (for a maximum of 24 months per patient since inclusion).)
- Quality of life (QoL) assessment(Screening visit, from cycle 13 (since completion of treatment with mFOLFIRINOX) onwards at each visit with test according to protocol, and at post-treatment termination visit (for a maximum of 24 months per patient since inclusion).)
- Overall survival (OS)(Since inclusion through study completion (for a maximum of 24 months per patient since inclusion).)
- Overall response rate (ORR)(Every 8 weeks from the beginning of the first treatment cycle (cycle 1) through study completion (for a maximum of 24 months per patient since inclusion).)
- Disease control rate (DCR)(Every 8 weeks from the beginning of the first treatment cycle (cycle 1) through study completion (for a maximum of 24 months per patient since inclusion).)
- Exploratory microbiome analysis(At screening, cycle 2 day 1 (each treatment cycle is 14 days), and cycle 5 day 1, and after discontinuation of last study treatment until disease progression (for a maximum of 24 months per patient since inclusion).)
- Progression-free survival (PFS)(Every 8 weeks from the beginning of the first treatment cycle (cycle 1) through study completion (for a maximum of 24 months per patient since inclusion).)
- Treatment impact on T-cell populations in the tumor and/or tumor periphery(At cycle 1 day 1 (each treatment cycle is 14 days), cycle 2 day 1, and cycle 5 day 1, and after discontinuation of last study treatment until disease progression (for a maximum of 24 months per patient since inclusion).)
- Treatment impact on the immunosuppressive myeloid cells in the TME and peripheral blood:(At cycle 1 day 1 (each treatment cycle is 14 days), cycle 2 day 1, and cycle 5 day 1, and after discontinuation of last study treatment until disease progression (for a maximum of 24 months per patient since inclusion).)