Evaluation of Tumor Treating Fields with Modified FOLFIRINOX in First-Line Treatment of Metastatic Pancreatic Adenocarcinoma
- Trial ID
- 2024-511459-16-00
- Protocol
- NOVOFFOX
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** of the combination of modFOLFIRINOX and Tumor Treating Fields (TTFields) using the NovoTTF-200T system as a first-line treatment for patients with metastatic pancreatic adenocarcinoma. This is clinically relevant as it aims to determine the safety profile of this novel therapeutic approach in a population with limited treatment options, potentially improving patient outcomes.
Secondary objectives include:
- To evaluate compliance with TTFields treatment.
- To evaluate the efficacy of TTFields treatment in combination with modFOLFIRINOX.
Participants
The clinical trial involves participants diagnosed with **pancreatic adenocarcinoma** with liver metastases, who have not received previous systemic treatment in the metastatic setting. The study population includes both male and female subjects aged 18 years and older. Participants are required to have adequate hematologic and organ function, as well as a life expectancy of more than three months. The trial does not include a vulnerable population. Participants must be able to operate the NovoTTF-200T System independently or with assistance and have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants have measurable disease as defined by RECIST 1.1, with at least one hepatic lesion accessible for biopsy. Prior chemotherapy or radiotherapy in the neoadjuvant or adjuvant setting is permissible if at least six months have elapsed since the last treatment. The trial population is not restricted by specific lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is a **Phase Ib-II**, non-randomized, open-label study designed to evaluate the safety of mFOLFIRINOX combined with Tumor Treating Fields (TTFields) using the NovoTTF-200T system as a first-line treatment for patients with metastatic pancreatic adenocarcinoma. The trial involves the administration of a combination of **oxaliplatin**, **calcium folinate**, **irinotecan hydrochloride**, and **fluorouracil**, all delivered via intravenous use. The study is expected to commence recruitment on January 15, 2025, and conclude by January 15, 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histological diagnosis of pancreatic adenocarcinoma, adequate hematologic and organ function, and a life expectancy of more than three months. Following the screening, participants will receive treatment cycles every 14 days, during which the total hours of TTField device functioning will be monitored. Follow-up visits will assess the toxicity profile, quality of life, progression-free survival, overall survival, overall response rate, and disease control rate. The end-of-study visit will occur after the completion of the treatment regimen or upon early termination.
The expected length of participant involvement is contingent upon the progression of the disease and the individual's response to treatment. Conditions that may lead to early termination from the study include the occurrence of treatment-emergent adverse events, disease progression, or any cause-related death. Participants must comply with all trial requirements, and women of childbearing potential must adhere to specific contraceptive guidelines. The trial's primary endpoint is the toxicity profile, measured by the rate of treatment-emergent adverse events using CTCAE v5.0, while secondary endpoints include quality of life assessments and survival metrics.
Treatment
The clinical trial involves the administration of **oxaliplatin**, a chemical compound used as an experimental medication. Oxaliplatin is provided in the pharmaceutical form coded as PHF00230MIG and is administered via **intravenous use**. The dosing schedule and frequency of administration are determined by the study protocol, ensuring adherence to safety and efficacy standards. Participant compliance is monitored throughout the trial to ensure accurate data collection and analysis.
**Calcium folinate**, also known as leucovorin calcium, is another experimental medication used in this study. It is administered in the pharmaceutical form coded as PHF00231MIG, also via intravenous use. The administration schedule is aligned with the study's objectives, and compliance is closely monitored to maintain the integrity of the trial results.
The trial also includes the administration of **irinotecan hydrochloride**, provided in the pharmaceutical form PHF00230MIG. This medication is delivered intravenously, with the dosing regimen specified in the study protocol. Monitoring of participant adherence to the dosing schedule is conducted to ensure the reliability of the trial outcomes.
Lastly, **fluorouracil**, known by synonyms such as 5-fluorouracil and 5-FU, is utilized in the trial. It is administered in the pharmaceutical form PHF00231MIG through intravenous use. The dosing schedule is carefully outlined in the study protocol, and participant compliance is tracked to ensure the accuracy and validity of the study data.
In addition to the experimental medications, the study employs standard-of-care therapy as a comparator treatment. The administration of these treatments is conducted under strict clinical guidelines, with participant compliance being a critical component of the trial's success. The study aims to evaluate the safety and efficacy of the combined treatment regimen for patients with metastatic pancreatic adenocarcinoma.
Efficacy
Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint focuses on the **toxicity profile** in patients with metastatic pancreatic adenocarcinoma treated with Tumor Treating Fields (TTFields) concomitantly with modFOLFIRINOX. This will be measured by the rate of patients experiencing treatment-emergent adverse events (TEAEs), utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Secondary endpoints include the total hours of TTField device functioning during each 14-day chemotherapy cycle, quality of life (QoL) assessed using the EORTC QLQ-30 questionnaire, progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR). PFS is defined as the time from the first administration of modFOLFIRINOX until disease progression based on CT scans according to RECIST 1.1 criteria or any cause-related death. OS is defined as the time from the first administration of modFOLFIRINOX until patient death. ORR is the percentage of patients achieving a complete response (CR) or partial response (PR) as the best overall response (BOR) according to RECIST 1.1. DCR is the percentage of patients with CR or PR and those with stable disease (SD) of at least 12 weeks duration as BOR according to RECIST 1.1.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 > 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 1.
- Amenable and assigned by the investigator to receive therapy with modFOLFIRINOX.
- Prior chemotherapy or radiotherapy on the neoadjuvant or adjuvant setting is allowed as long as at least six months have elapsed since last chemotherapy treatment.
- Able to operate the Novo TTF-200T System independently or with the help of a caregiver.
- Adequate hematologic and organ function, defined by the following laboratory test results, obtained during the screening period and before C1D1. a. WBC > 2.5 x 109/L. b. ANC > 1.5 x 109/L without granulocyte colony-stimulating factor support. c. Platelet count > 100 x 109/L. without transfusion. d. Hemoglobin > 9 g/dL. e. Albumin > 2.5 g/dL. f. Serum bilirubin < 1.5 times de upper limit of normal (ULN); patients with known Gilbert´s disease may have a bilirubin value < 3 x ULN. g. INR and aPTT < 1.5 x ULN. h. AST, ALT, < 5 x ULN. i. Serum creatinine < 1,5 x ULN or Creatinine Clearance > 30ml/min (calculated using Cockcroft-Gault formula).
- For women of childbearing potential: Negative serum pregnancy test within 14 days prior to C1D1. Agreement to remain abstinent (refrain from heterosexual intercourse) or use of contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 180 days after the last study treatment. A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
Exclusion Criteria
- 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 >90%), 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.
- Pregnant and lactating women.
- Patients who have received brivudine, sorivudine or analogues 4 weeks prior to Fluoracile administration.
- Serious co-morbidities, including but not limited to: a. History of significant cardiovascular disease unless the disease is well controlled. Significant cardiac disease includes second/third degree hart block; significant ischemic heart disease; poorly controlled hypertension; congestive heart failure of the New York Heart Association (NYHA) Class II or worse. b. History of cerebrovascular accident (CVA) within 3 months prior to randomization or that is not stable. c. Active infection or serious underlying medical condition that would impair the ability of the patient to receive protocol therapy. d. History of any psychiatric condition that might impair patient´s ability to understand or comply with the requirements of the study or to provide consent.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Recruiting | 01 Oct 2025 | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CALCIUM FOLINATE | Test | PHF00231MIG | INTRAVENOUS USE | — | — | SCP107133400 |
OXALIPLATIN | Test | PHF00230MIG | INTRAVENOUS USE | — | — | SCP128961 |
FLUOROURACIL | Test | PHF00231MIG | INTRAVENOUS USE | — | — | SCP1165178 |
IRINOTECAN | Test | PHF00230MIG | INTRAVENOUS USE | — | — | SCP139021 |