Table of Contents

• Clinical trial overview
• Cancer types being studied
• Trial phases and study sizes
• What the trials measure
• Who may be included
• Examples of study designs

Clinical trial overview

The source data shows that Levoleucovorin is being studied in cancer trials as part of combination treatment plans.^[1] These studies are focused on whether the treatment plans help people live longer, keep the cancer under control, or improve the chance of successful surgery.^[1][2]

Most of the trials are interventional studies, which means the researchers give a treatment and then measure the results.^[1] The trials in the data include authorised studies and one completed study.^[1][2]

Cancer types being studied

Levoleucovorin is being studied in several cancers of the digestive system.^[1] These include pancreatic ductal adenocarcinoma, colon cancer, rectal cancer, small bowel adenocarcinoma, gastric cancer, and gastroesophageal junction cancer.^[1][2]

Some studies focus on cancer after surgery, such as resected pancreatic adenocarcinoma and stage III colon cancer after resection.^{[2][3] Other studies include locally advanced disease, recurrent disease, or metastatic disease, which means the cancer is harder to treat because it is more spread out or has returned.[1][4]}

Trial phases and study sizes

The studies in the data are mainly Phase 2 and Phase 3, with one Phase 4 study.^{[1][2] Phase 2 studies usually look more closely at whether a treatment seems helpful, while Phase 3 studies compare treatment strategies in larger groups.[3]}

Enrollment ranges from small studies with 30 patients to larger studies with 973 patients.^{[1][2] This shows that the research includes both smaller focused studies and larger confirmatory trials.[1][3]}

What the trials measure

The main endpoints, or results the researchers want to measure, include overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and relapse-free survival (RFS).^{[1][2] These terms describe how long patients live, how long the cancer does not worsen, or how long it stays away after treatment.[1][2]}

Some trials also measure surgery-related outcomes, such as the rate of R0 resection, which means surgery removes all visible cancer.^[3] One study looks at peritoneal metastasis-free survival, which is the time before cancer spreads to the lining of the abdomen.^[4]

Other studies use shorter-term measures, such as being alive and free of progression at a set time point like 85 days or 6 months.^{[5][6] One trial also measures treatment tolerability, including acute digestive non-toxicity after radiotherapy, which means side effects affecting the digestive system are being checked closely.[6]}

Who may be included

The included patient groups are different from trial to trial.^[1] Some trials are for people after surgery, some are for people with cancer that has returned, and some are for people with metastatic disease.^[2][4]

Some studies have extra entry rules, such as HLA-A2 positive status, HER2-negative disease, or FGFR2b overexpression.^{[1][5] These are tumor or patient features used to decide who can join a specific study.[1][5]}

One study focuses on patients aged 70 and older after stage III colon or upper rectal cancer resection.^[3] Another study includes patients with obstructive colon cancer who first had a stoma, which is a surgically created opening to help stool leave the body.^[4]

Examples of study designs

In one Phase 2 pancreatic cancer study, researchers are comparing maintenance treatment with OSE2101 plus FOLFIRI against FOLFIRI alone after induction therapy without disease progression.^[1] The main outcome is overall survival at 12 months.^[1]

In a Phase 3 rectal cancer study, researchers are testing chemotherapy followed by pelvic reirradiation against chemotherapy alone before surgery, and the main endpoint is the proportion of curative surgery.^[3] In a Phase 3 colon cancer study for older adults, the main endpoint is relapse-free survival at 3 years after surgery.^[3]

In a Phase 2 metastatic pancreatic cancer study, the trial is testing a first-line treatment plan that includes NALIRIFOX followed by 5-FU/leucovorin maintenance, and a second step that adds ciprofloxacin to gemcitabine-based chemotherapy.^[5] The trial measures 6-month progression-free survival in the first step and 6-month overall survival in the second step.^[5]

In a completed Phase 2 gastric and gastroesophageal junction cancer study, Levoleucovorin appears in a perioperative treatment plan with FLOT and bemarituzumab, and the study measured complete pathological response after surgery.^[7]