Phase II Randomized Trial of Modified FOLFIRINOX and FOLFOX Regimens in Locally Advanced or Metastatic Small Bowel Adenocarcinoma

The primary objective of this Phase II randomized trial is the **assessment** of the percentage of patients with **small bowel adenocarcinoma** who are alive without progression at 8 months. This objective is clinically relevant as it provides insight into the efficacy of the treatment regimens being evaluated, which include modified FOLFIRINOX and FOLFOX, in delaying disease progression in patients with locally advanced or metastatic conditions.

Secondary objectives include evaluating overall survival, progression-free survival, time to treatment failure, and response rates during first-line treatment. Additionally, the study aims to assess treatment tolerance and quality of life during treatment. Another focus is on progression-free survival in the second line of treatment for the total population and by specific second-line treatments. These objectives are crucial for understanding the broader impact of the treatment regimens on patient outcomes and quality of life.

The clinical trial involves participants diagnosed with **small bowel adenocarcinoma**, specifically targeting individuals with histologically proven adenocarcinoma of the small intestine, including the duodenum, jejunum, and ileum. The study population comprises both male and female subjects, with an age range that includes adults and older adults. Participants are required to have a metastatic or locally advanced unresectable tumor with curative intent and must not have received first-line chemotherapy previously. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less for those under 70 years, and 0 or 1 for those over 70 years, with a life expectancy estimated at over 3 months. The trial population selection criteria also consider the presence of measurable lesions according to RECIST 1.1 criteria. The sponsor has not provided the total number of participants involved in the study. The trial includes a vulnerable population, indicating additional ethical considerations in the study design. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **controlled**, Phase II study to evaluate the efficacy of modified FOLFIRINOX and FOLFOX regimens in the treatment of locally advanced or metastatic **small bowel adenocarcinoma**. The primary objective is to assess the percentage of patients alive without progression at 8 months. The trial will involve the administration of **calcium levofolinate**, **irinotecan hydrochloride trihydrate**, **oxaliplatin**, and **fluorouracil** as solutions for infusion, with specific dosing regimens tailored to each participant's condition. The trial is expected to last until October 2029, with recruitment starting in October 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically proven adenocarcinoma of the small intestine, metastatic or locally advanced unresectable tumor, and measurable lesions according to RECIST 1.1 criteria. Follow-up visits will be scheduled to monitor the participants' response to treatment and any adverse effects. The end-of-study visit will conclude the trial for each participant, assessing the primary and secondary endpoints, including survival and progression-free survival.

The expected length of participant involvement is up to 36 months, depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include significant disease progression, unacceptable toxicity, or withdrawal of consent by the participant. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of several **experimental medications** in the form of solutions for infusion. **Calcium Levofolinate** is utilized as a supplement in the study. It is administered via **intravenous infusion** with a maximum daily dose of 400 mg/m² and a total dose of 400 mg/m². The treatment period extends up to 36 weeks. This compound is chemically derived and is not formulated for pediatric use.

**Irinotecan Hydrochloride Trihydrate** is employed as a chemotherapy agent. It is delivered through an **intravenous route** with a maximum daily and total dose of 180 mg/mL. The treatment duration is capped at 36 weeks. This chemical substance is also not intended for pediatric formulations.

**Oxaliplatin** is another chemotherapy agent used in the trial. It is administered intravenously with a maximum daily and total dose of 85 mg/m². The treatment period is limited to 36 weeks. Like the other substances, it is chemically derived and not suitable for pediatric use.

**Fluorouracil** is included as a chemotherapy treatment. It is administered via **intravenous bolus injection or IV infusion** with a maximum daily dose of 400 mg/m² and a total dose of 400 mg/m². Additionally, another regimen involves an intravenous route with a maximum daily dose of 1200 mg/m² and a total dose of 2400 mg/m². The treatment duration for both regimens is up to 36 weeks. This chemical compound is not formulated for pediatric use.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the efficacy of these treatments in patients with locally advanced or metastatic small bowel adenocarcinoma.

The efficacy of the clinical trial will be assessed primarily by evaluating the percentage of patients alive without progression at 8 months. This primary endpoint will be measured to determine the effectiveness of the treatment regimens being tested. Secondary endpoints include overall survival and progression-free survival, which will provide additional insights into the long-term benefits of the treatment. The trial involves patients with histologically proven adenocarcinoma of the small intestine, specifically those with metastatic or locally advanced unresectable tumors. The trial will utilize the RECIST 1.1 criteria to assess measurable lesions, ensuring standardized evaluation of tumor response. The study is designed as a Phase II randomized trial, comparing modified FOLFIRINOX and FOLFOX regimens in the treatment of locally advanced or metastatic small bowel adenocarcinoma. The trial is expected to conclude by October 2029, with recruitment having started in October 2023.