Phase II Randomized Study of Gemcitabine Versus Reduced-Dose Gemcitabine and Paclitaxel Albumin-Bound in Frail Patients with Unresectable Pancreatic Cancer

The primary objective of this randomized phase II study is to evaluate the efficacy of **gemcitabine** at a standard dose compared to a reduced-dose combination chemotherapy regimen, specifically **gemcitabine** combined with **paclitaxel albumin-bound** (GemNab), in patients with non-resectable pancreatic cancer who are considered fragile and unfit for full-dose combination chemotherapy as a first-line treatment. This study is clinically relevant as it aims to determine the optimal treatment strategy for a vulnerable patient population, potentially improving therapeutic outcomes and quality of life for those who cannot tolerate more aggressive chemotherapy regimens.

The clinical trial focuses on evaluating treatment options for patients with **pancreatic cancer** who are unfit or not candidates for full-dose combination chemotherapy. The study population includes both male and female participants aged 18 years and older. Participants must have a histopathologically or cytologically verified adenocarcinoma of the pancreas that is non-resectable, either locally advanced or metastatic. The trial does not involve a vulnerable population. Participants are required to have a performance status of 2 or less and adequate hematologic and organ function. The sponsor has not provided information regarding the total number of participants. Selection criteria include the resolution of prior chemotherapy toxicity to CTCAE grade 1 or less, and the ability to provide informed consent. Fertile participants must use adequate contraceptives. Lifestyle factors such as diet and physical activity are not specified in the trial details.

The clinical trial is designed as a **randomized**, phase II study to evaluate the efficacy of standard dose **gemcitabine** versus a reduced dose combination chemotherapy in patients with non-resectable **pancreatic cancer**. The trial employs a **double-blind** methodology to ensure unbiased results, with participants randomly assigned to receive either the standard treatment or the reduced-dose combination. The primary endpoint of the study is **Progression Free Survival (PFS)**, while secondary endpoints include **Overall Survival (OS)**, response rate, number of hospitalizations during treatment, quality of life assessments, and cumulative worst toxicity during treatment.

The trial is expected to last until December 2026, with recruitment having commenced in June 2023. Participants will be involved in the study for a maximum treatment period of 24 weeks. The study includes several key visits: an initial screening visit to confirm eligibility based on criteria such as age, performance status, and adequate organ function; regular follow-up visits to monitor treatment response and adverse events; and an end-of-study visit to assess final outcomes and gather data on the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or withdraw consent.

Inclusion criteria for the study require participants to be 18 years or older, with a confirmed diagnosis of non-resectable pancreatic cancer, and a performance status of 2 or less. Adequate hematologic and organ function must be demonstrated prior to enrollment. Exclusion criteria are not explicitly detailed in the provided data. The study aims to provide valuable insights into the optimal treatment strategy for this patient population, potentially influencing future therapeutic approaches for non-resectable pancreatic cancer.

The clinical trial involves the administration of **Gemcitabine Accord**, a **solution for infusion** with a concentration of 100 mg/ml. This experimental medication is administered **intravenously**. The dosing regimen for Gemcitabine Accord is set at a maximum daily dose of 1000 mg/m², with a total maximum dose of 72000 mg/m² over a treatment period of 24 weeks. The active substance, **gemcitabine**, is of chemical origin and is provided by Accord Healthcare B.V. This formulation is not a pediatric formulation and is used as a test treatment in the study.

Another treatment used in the trial is **Abraxane**, a **powder for dispersion for infusion** containing **paclitaxel albumin-bound** as the active substance. This comparator treatment is also administered **intravenously**. The dosing schedule for Abraxane involves a maximum daily dose of 100 mg/m², with a total maximum dose of 7200 mg/m² over a 24-week period. The active substance is categorized under Specified Substance Group 1 and is supplied by Bristol-Myers Squibb Pharma EEIG. This formulation is not intended for pediatric use.

A second formulation of **Gemcitabine Accord** is also utilized in the trial, with a similar **solution for infusion** form and concentration of 100 mg/ml. This formulation is administered **intravenously** with a maximum daily dose of 800 mg/m² and a total maximum dose of 57600 mg/m² over 24 weeks. The active substance, **gemcitabine**, is of chemical origin and provided by Accord Healthcare B.V. This formulation is also not a pediatric formulation and serves as a test treatment in the study.

The efficacy of the clinical trial will be assessed using several key endpoints. The primary endpoint is **Progression Free Survival (PFS)**, which will be measured to determine the length of time during and after the treatment that a patient lives with the disease without it getting worse. Secondary endpoints include Overall Survival (OS), which evaluates the duration of time from the start of treatment until death from any cause, and the Response Rate, which measures the proportion of patients whose cancer shrinks or disappears after treatment. Additionally, the number of hospitalizations during treatment will be recorded, and Quality of Life will be assessed using the EORTC QLQ-C30 questionnaire at baseline and after 8, 16, and 24 weeks. Cumulative worst toxicity during treatment will also be evaluated, focusing on adverse events of grade 3 or higher according to CTCAE version 5.0.