What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, such as those involving fluoropyrimidines (5-FU), leucovorin, irinotecan, and bevacizumab, are associated with a range of side effects. Fluoropyrimidines can cause diarrhea, mucositis, and hand-foot syndrome. Irinotecan is known for causing severe diarrhea and neutropenia. Bevacizumab, an anti-angiogenic agent, can lead to hypertension, increased risk of bleeding, and gastrointestinal perforation. Combining these agents can increase the risk and severity of these side effects, necessitating careful management and monitoring during treatment.

What prior FDA approvals exist?

The FDA has approved several fluoropyrimidine-based therapies for the treatment of colorectal cancer. Notably, 5-FU (fluorouracil) combined with leucovorin (LV) has been a cornerstone of treatment. Additionally, combination regimens such as FOLFIRI (5-FU, LV, and irinotecan) and FOLFOX (5-FU, LV, and oxaliplatin) have been widely used. Bevacizumab, an anti-VEGF monoclonal antibody, is often added to these regimens to enhance efficacy. These treatments aim to improve survival and disease-free outcomes in patients with metastatic colorectal cancer.

What other types of research exist?

Promising novel alternatives to NUC-3373 for colorectal cancer patients include TAS-102 (trifluridine/tipiracil), which has shown efficacy in patients with advanced or recurrent colorectal cancer refractory to standard therapies. Additionally, combination therapies such as TAS-102 with bevacizumab, cetuximab, or panitumumab have demonstrated potential in preclinical studies. These alternatives offer new avenues for treatment, especially for patients who have not responded to traditional fluoropyrimidine-based therapies.

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Fluoropyrimidine

NUC-3373 + Chemotherapy for Colorectal Cancer

Phase 2

Waitlist Available

Research Sponsored by NuCana plc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up assessed from baseline to 30 days after last dose of study drug

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two combinations of cancer drugs on patients with advanced colorectal cancer that can't be removed by surgery. One combination includes a new drug called NUC-3373, and the other uses a traditional drug. The goal is to see which combination works better at killing cancer cells and stopping their growth.

Who is the study for?

This trial is for adults with advanced colorectal cancer that can't be removed by surgery. They must have had previous chemotherapy, know their UGT1A1 status (or agree to testing), and not have certain genetic mutations or serious health conditions. Women of childbearing age need a negative pregnancy test and must use effective contraception.

What is being tested?

The study compares NUC-3373 combined with leucovorin, irinotecan, and bevacizumab against the standard treatment using 5-FU instead of NUC-3373. Patients are randomly assigned to one of three groups receiving different schedules of these drugs to see which works best.

What are the potential side effects?

Possible side effects include reactions related to the immune system, fatigue, digestive issues like nausea or diarrhea, increased risk of infections due to lowered white blood cells, bleeding complications from low platelets, anemia from low red blood cell counts, liver function changes, and potential skin sensitivity.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ assessed from baseline to 30 days after last dose of study drug

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~assessed from baseline to 30 days after last dose of study drug

This trial's timeline: 3 weeks for screening, Varies for treatment, and assessed from baseline to 30 days after last dose of study drug for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of patients achieving progress-free survival (PFS)

Secondary study objectives

Number of patients achieving a reduction in tumour volume

Number of patients reporting treatment-emergent adverse events (TEAEs)

Number of patients surviving

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: NUFIRI-bev on a Q2W NUC-3373 scheduleExperimental Treatment4 Interventions

Arm B: Study treatment will be administered in 28-day cycles as follows: 1. Bevacizumab 5 mg/kg on Days 1 and 15: * 90 minutes for the first dose * 60 minutes for the second dose (if first dose is tolerated) * 30 minutes for subsequent doses (if second dose is tolerated) 2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1 and 15. 3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15. 4. NUC-3373 1500 mg/m2 over 120 minutes on Days 1 and 15.

Group II: NUFIRI-bev on a Q1W NUC-3373 scheduleExperimental Treatment4 Interventions

Arm A: Study treatment will be administered in 28-day cycles as follows: 1. Bevacizumab 5 mg/kg on Days 1 and 15: * 90 minutes for the first dose * 60 minutes for the second dose (if first dose is tolerated) * 30 minutes for subsequent doses (if second dose is tolerated) 2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1, 8, 15, and 22. 3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15. 4. NUC-3373 1500 mg/m2 over 120 minutes on Days 1, 8, 15, and 22.

Group III: FOLFIRI-bev on a Q2W scheduleActive Control4 Interventions

Arm C: Study treatment will be administered in 28-day cycles as follows: 1. Bevacizumab 5 mg/kg on Days 1 and 15: * 90 minutes for the first dose * 60 minutes for the second dose (if first dose is tolerated) * 30 minutes for subsequent doses (if second dose is tolerated) 2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1 and 15. 3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15. 4. 5-FU 400 mg/m2 bolus on Days 1 and 15. 5. 5-FU 2400 mg/m2 infusion over 46 hours on Days 1 and 15.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Irinotecan

2017

Completed Phase 3

~2580

Leucovorin

2005

Completed Phase 4

~6010

Bevacizumab

2013

Completed Phase 4

~5540

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for colorectal cancer include fluoropyrimidines like 5-FU and its novel counterpart NUC-3373, which inhibit thymidylate synthase, disrupting DNA synthesis and cell division. Leucovorin enhances the binding of 5-FU to its target enzyme, increasing its efficacy. Irinotecan inhibits topoisomerase I, preventing DNA replication and transcription, leading to cell death. Bevacizumab is an anti-angiogenic agent that inhibits VEGF, reducing blood supply to tumors and hindering their growth. These mechanisms are crucial as they target different aspects of cancer cell survival and proliferation, offering a multi-faceted approach to treatment and potentially improving patient outcomes.