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?
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Patients will receive the following medication in 14-day cycles: ModFOLFIRINOX * Folic acid (Leucovorin) 400mg/m2 (D,L, racemic form) or 200mg/m2 (L-isomer form) * 5-fluorouracil (5Fu) 2400 mg/m2 * Oxaliplatin 85mg/m2 * Irinotecan 150-180mg/m2 Combined with TTFields, which is a portable battery operated system intended for continuous home use (at least 18h/day) which delivers TTFields at a frequency of 150kHz to produces electric forces intended to disrupt cancer cell division.
Clínica Universidad de Navarra
Pamplona, Navarre, Spain
RECRUITINGHospital Universitario de Cruces
Barakaldo, Vizcaya, Spain
NOT_YET_RECRUITINGHospital de Galdakao
Galdakao, Vizcaya, Spain
NOT_YET_RECRUITINGFundación Jiménez-Díaz
Madrid, Spain
NOT_YET_RECRUITINGHospital Universitario de Araba
Vitoria-Gasteiz, Álava, Spain
NOT_YET_RECRUITINGToxicity profile in patients with mPDAC treated at 1L with TTFields concomitantly with modFOLFIRINOX
Toxicity profile measured by the rate of patients with treatment-emergent adverse events (TEAEs), using CTCAE v5.0
Time frame: 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)
Total hours with TTField device functioning during every 14 days chemotherapy cycle
Total account of hours with TTField device functioning during every 14days chemotherapy cycle in the ITT population.
Time frame: 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
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of 30 items (EORTC QLQ-30). Questions 1-28: scale from 1 to 4, where 1 means a better quality of life and 4 indicates a worse quality of life; questions 29-30: scale from 1 to 7, where low scores indicate poorer health and quality of life, while high scores indicate better health and quality of life.
Time frame: 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).
Progression-free survival (PFS)
The time in months from first modFOLFIRINOX administration until disease progression based on CT scan collected on the study according to RECIST 1.1 criteria or any cause related death, whichever occurs first.
Time frame: 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).
Overall survival (OS)
The time from first modFOLFIRINOX administration until patient death (if it occurs).
Time frame: Since inclusion through study completion (for a maximum of 24 months per patient since inclusion).
Overall response rate (ORR)
The percentage of patients with complete response (CR) or partial response (PR) as best overall response (BOR) according to RECIST 1.1.
Time frame: 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)
The percentage of patients with CR or PR and the percentage of subjects with stable (SD) of at least 12 weeks duration as BOR according to RECIST 1.1.
Time frame: 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
Exploratory analyses on T-cell populations may include but will not be limited to Tumor-infiltrating lymphocytes (TILS) percentage measurement (immunohistochemistry (IHC)), percentage of different T-cell populations (e.g. CD8 or CD3) and RNAseq (antitumoral gene signatures evaluation), PD1-PDL1 expression (IHC).
Time frame: 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:
Exploratory analyses on myeloid cells may include but will not be limited to RNAseq (immunosuppressive gene signature evaluation) and cytometry (changes on peripheral blood mononuclear cells).
Time frame: 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).
Exploratory microbiome analysis
Evaluation of microbiome communities via metagenomics sequencing in stool samples and identification of bacterial-derived metabolites in plasma.
Time frame: 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).
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