Irinotecan Clinical Trials

What Is Irinotecan?

Irinotecan is an FDA-approved medication for metastatic colorectal cancer and colon cancer. It is a chemotherapy drug that works by interfering with the DNA (genetic material) of cancer cells. Specifically, irinotecan is a topoisomerase I inhibitor, which means it blocks an enzyme essential for DNA replication in cancer cells. This action can slow down the growth and spread of cancer cells and ultimately cause them to die.

In addition to its approved uses, irinotecan is being investigated in clinical trials for a wide range of other cancers. These studies aim to understand its effectiveness and safety, often in combination with other anti-cancer drugs or therapies.

Uses and Conditions Under Study

Irinotecan is extensively studied for various cancers, with a total of 1344 trials and 177,233 participants. The first trial began on April 30, 2002, and the latest is projected to conclude on May 26, 2026. The National Cancer Institute (NCI) is a leading sponsor with 61 trials.

• Colorectal Cancers: Irinotecan is FDA-approved for colorectal cancer and metastatic colorectal cancer, which is the third most common malignant tumor worldwide. Approximately 70% of distant metastases occur in the liver. A total of 329 trials investigate irinotecan for colorectal cancer, metastatic colorectal cancer, and colorectal neoplasms.
• Gastric and Esophageal Cancers: Gastric cancer is a significant cause of mortality, with metastatic patients often having a short survival time. Esophageal cancer is also a common malignant disease, particularly in China, where esophageal squamous cell carcinoma is prevalent. Irinotecan is being studied in 70 trials for gastric cancer and 41 trials for esophageal cancer.
• Pancreatic Cancer: This is a highly malignant cancer with a very poor prognosis, characterized by rapid progression and difficult early diagnosis. Irinotecan is being evaluated in 62 trials for pancreatic cancer, often in combination with other therapies like FOLFIRINOX.
• Lung Cancers: Small cell lung cancer (SCLC) accounts for about 15% of all lung cancer diagnoses and is known for its rapid proliferation and early metastasis. Irinotecan is under investigation for lung cancer in 32 trials and for small cell lung cancer in 22 trials.
• Neuroblastoma: As the most common extracranial pediatric solid tumor, neuroblastoma primarily affects infants and toddlers. Irinotecan is being studied in 28 trials for this condition, often in combination with other drugs like temozolomide and naxitamab.
• Other Solid Tumors: Irinotecan is also being investigated in 39 trials for unspecified adult solid tumors, protocol specific, indicating its broad potential application across various advanced cancers.

Dosing

Irinotecan has been studied in several forms and dosages, often as part of combination therapies for various cancers. The drug is commonly administered as an intravenous (IV) infusion, as noted in multiple trial descriptions.

One common formulation is irinotecan hydrochloride, which is frequently used in chemotherapy regimens such as FOLFIRI (a combination with fluorouracil and leucovorin). Another significant form is irinotecan liposome injection, sometimes referred to as "Liposomal Irinotecan" or Onivyde®. This liposomal formulation aims to improve drug delivery and stability.

Oral forms of irinotecan have also been investigated, particularly in pediatric patients with neuroblastoma, where it has been studied in a three-drug combination with vincristine and temozolomide. Additionally, specialized delivery methods such as irinotecan-eluting beads for hepatic arterial infusion chemotherapy have been explored for liver metastases.

Dosages of irinotecan vary widely depending on the specific cancer, combination therapy, and patient characteristics. Studies have explored different strengths, including specific milligram per square meter (mg/m²) doses such as 24 mg/m², 36 mg/m², and 42 mg/m² for certain investigational drugs combined with irinotecan. Intraperitoneal administration of irinotecan has been tested at doses ranging from 50 mg to 250 mg. Some trials also investigate "high doses" versus "standard doses" of irinotecan, and dose adjustments may be based on genetic factors like UGT1A1 genotype, which can affect drug metabolism.

Side Effects

In clinical trials, the most common side effect reported by patients taking Irinotecan was diarrhea, affecting 63.6% of patients compared to 53.9% of those on placebo. These findings are based on data from multiple clinical trials involving up to 2188 patients in the Irinotecan treatment arm.

Other common side effects experienced by patients on Irinotecan, with a notable difference compared to placebo, included:

• Neutropenia (a decrease in white blood cells), which occurred in 46.2% of patients taking Irinotecan versus 35.2% on placebo.
• Fatigue, reported by 43.0% of patients on Irinotecan compared to 36.4% on placebo.
• Stomatitis (inflammation of the mouth), affecting 37.0% of patients taking Irinotecan versus 24.3% on placebo.
• Decreased appetite, observed in 35.6% of patients on Irinotecan compared to 26.1% on placebo.
• Hypertension (high blood pressure), which occurred in 24.7% of patients taking Irinotecan versus 9.1% on placebo.
• Epistaxis (nosebleed), reported by 20.7% of patients on Irinotecan compared to 9.6% on placebo.

Some side effects, such as nausea (50.8% on Irinotecan vs 51.0% on placebo) and vomiting (31.6% on Irinotecan vs 30.8% on placebo), were reported at similar rates in both Irinotecan and placebo groups, indicating they may not be directly attributable to the drug.

Clinical Trial Results

Colorectal Cancer

In a study (NCT00022698) evaluating Irinotecan in combination with Capecitabine for locally advanced, recurrent, or metastatic colorectal cancer, patients received either an initial or amended regimen. The median overall survival was 22.9 months for patients on the initial regimen and 20.5 months for those on the amended regimen. The percentage of patients surviving one year was 67% in the initial regimen group and 71% in the amended regimen group. The time until disease progression was a median of 6.1 months for the initial regimen and 7.6 months for the amended regimen. Tumor response rates were 40% for the initial regimen and 42% for the amended regimen.

Esophageal Cancer

A trial (NCT00033657) compared a regimen of Cisplatin, Irinotecan, and radiation therapy (Arm A) to Paclitaxel, Cisplatin, and radiation therapy (Arm B) in patients with esophageal cancer. Patients in the Irinotecan arm (Arm A) had a median overall survival of 35.0 months, significantly longer than the 21.0 months in the Paclitaxel arm (Arm B). Recurrence-free survival was also notably longer in the Irinotecan arm, with a median of 39.8 months compared to 12.4 months in the Paclitaxel arm.

Metastatic Pancreatic Cancer

A study (NCT00042939) investigated Irinotecan and Docetaxel, with or without Cetuximab, for metastatic pancreatic cancer. Patients receiving Irinotecan and Docetaxel alone (Arm A) had a median overall survival of 6.5 months, while those who also received Cetuximab (Arm B) had a median overall survival of 5.3 months. Progression-free survival was 3.9 months for Arm A and 4.5 months for Arm B. The proportion of patients showing an objective tumor response was 4.5% in Arm A and 7% in Arm B.

Extensive-Stage Small Cell Lung Cancer

Two trials examined Irinotecan-containing regimens for extensive-stage small cell lung cancer.

In one study (NCT00045162), Cisplatin plus Irinotecan was compared to Cisplatin plus Etoposide. Patients treated with Cisplatin plus Irinotecan had a median overall survival of 9.9 months, slightly longer than the 9.1 months for those on Cisplatin plus Etoposide. Progression-free survival was also slightly longer with Irinotecan, at 5.7 months compared to 5.2 months.

Another study (NCT00057837) compared an Irinotecan/Cisplatin/Etoposide regimen (PIE) to a Topotecan/Etoposide/Cisplatin/G-CSF regimen (PET). The PET regimen showed a median overall survival of 11.9 months, compared to 11.0 months for the PIE regimen

Currently Recruiting Trials

• A Phase 3 trial, NCT06998940, is comparing chemotherapy with or without panitumumab for unresectable, locally advanced, or metastatic pancreatic cancer without KRAS mutations. This study includes standard chemotherapy regimens that feature nanoliposomal Irinotecan or Irinotecan. It plans to enroll 94 participants.
• Another Phase 3 study, NCT07409272, is evaluating the effectiveness and safety of setidegrasib when combined with mFOLFIRINOX or NALIRIFOX chemotherapies (both containing Irinotecan) in people with pancreatic cancer. This trial aims to enroll 614 participants.
• For patients with advanced colorectal liver metastases, a Phase 2 trial, NCT07441369