What is the mechanism of action of this treatment?

TAS-102, a combination of trifluridine and tipiracil, works by incorporating trifluridine into DNA, thereby inhibiting cancer cell proliferation, while tipiracil prevents trifluridine degradation, enhancing its efficacy. Irinotecan inhibits topoisomerase I, an enzyme crucial for DNA replication, leading to DNA damage and cancer cell death. Bevacizumab, an immunotherapy agent, targets vascular endothelial growth factor (VEGF), inhibiting angiogenesis, which is the formation of new blood vessels that tumors need to grow. These mechanisms are vital for colon cancer patients as they collectively disrupt cancer cell growth, enhance DNA damage, and cut off the tumor's blood supply, thereby improving treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for colon cancer, such as TAS-102, Irinotecan, and Bevacizumab, have several known side effects. Chemotherapy agents like TAS-102 and Irinotecan can cause neutropenia, anemia, fatigue, diarrhea, nausea, and vomiting. Bevacizumab, an immunotherapy agent, can lead to hypertension, proteinuria, bleeding, thromboembolic events, and gastrointestinal perforations. Combining these treatments may increase the severity and frequency of these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for metastatic colorectal cancer that involve chemotherapy and immunotherapy. Bevacizumab, an anti-VEGF monoclonal antibody, is often combined with chemotherapeutic agents like fluorouracil, irinotecan, and oxaliplatin. TAS-102 (trifluridine/tipiracil) has also been approved for patients with metastatic colorectal cancer who have been previously treated with standard chemotherapies. Additionally, combinations such as FOLFOX (folinic acid, fluorouracil, and oxaliplatin) and FOLFIRI (folinic acid, fluorouracil, and irinotecan) with Bevacizumab are commonly used. These treatments aim to inhibit tumor growth and improve survival outcomes in patients with advanced disease.

What other types of research exist?

Promising novel alternatives for colon cancer treatment in 2024 include: 1) Immunotherapy combinations such as nivolumab plus ipilimumab, which have shown efficacy in various cancers including colorectal cancer. 2) Targeted therapies like encorafenib combined with cetuximab for BRAF V600E-mutant metastatic colorectal cancer. 3) Newer agents like regorafenib and trifluridine/tipiracil (Lonsurf) in combination with other drugs. 4) Emerging treatments involving personalized medicine approaches, such as CAR-T cell therapy and other forms of adoptive cell transfer.

← Back to Search

Monoclonal Antibodies

Combination Chemotherapy for Colorectal Cancer

Phase 2

Waitlist Available

Led By Christos Fountzilas, MD

Research Sponsored by Roswell Park Cancer Institute

Eligibility Criteria Checklist

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

Must have

Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Prior treatment with a fluoropyrimidine (5-fluorouracil [5-FU] or capecitabine) and oxaliplatin in the metastatic/unresectable setting OR, recurrence within 12 months of adjuvant therapy with a regimen that included oxaliplatin

Must not have

Prior treatment with TAS-102 or irinotecan

Anti-cancer therapy within 2 weeks of the planned first dose of study medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years post-treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of three drugs to treat advanced colorectal cancer. It targets patients whose cancer has spread or cannot be surgically removed. The drugs work together to kill cancer cells, block their growth, and help the immune system fight the cancer. Oxaliplatin is a new drug that has been recently added to initial treatments for advanced colorectal cancer.

Who is the study for?

This trial is for adults with advanced colorectal cancer that has spread or can't be surgically removed. Participants must have had prior treatment with certain chemotherapy drugs, have good physical function (ECOG 0-1), and meet specific blood count and organ function criteria. Pregnant women, those with recent major surgery, uncontrolled high blood pressure, serious heart conditions, or untreated brain metastases cannot join.

What is being tested?

The study tests a combination of TAS-102 (a chemotherapy drug), irinotecan (another chemo drug), and bevacizumab (an immunotherapy agent) in patients who've previously been treated for metastatic or unresectable colorectal cancer. The goal is to see if this combo is more effective than traditional treatments.

What are the potential side effects?

Possible side effects include fatigue, nausea, diarrhea from the chemotherapy drugs TAS-102 and irinotecan; high blood pressure and increased risk of bleeding from bevacizumab; as well as potential allergic reactions to any of the medications used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am fully active or can carry out light work.

Select...

I've been treated with specific chemotherapy drugs for my advanced cancer or it came back within a year after treatment.

Select...

My colorectal cancer cannot be removed by surgery and has spread.

Select...

My kidney function, measured by creatinine levels, is within the normal range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have previously been treated with TAS-102 or irinotecan.

Select...

I haven't had cancer treatment in the last 2 weeks.

Select...

I have brain metastases that have not been treated.

Select...

I have Gilbert's syndrome.

Select...

I am currently pregnant or breastfeeding.

Select...

I have not had severe bleeding in the last 4 weeks.

Select...

I have not had major surgery in the last 4 weeks.

Select...

I have an infection that could make treatment risky.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years post-treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years post-treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years post-treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Median progression free survival (PFS)

Secondary study objectives

Aggregate rates of adverse events

Disease-specific survival (DSS)

Median overall survival (OS)

+1 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (irinotecan, bevacizumab, TAS-102)Experimental Treatment3 Interventions

Patients receive irinotecan IV over 90 minutes and bevacizumab IV over 10 minutes on days 1 and 15. Patients also receive trifluridine and tipiracil hydrochloride PO BID on days 2-6 and 16-20. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Irinotecan

2017

Completed Phase 3

~2590

Bevacizumab

2013

Completed Phase 4

~5540

Trifluridine and Tipiracil Hydrochloride

2019

Completed Phase 2

~180

0 / 12Eligibility criteria met

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

TAS-102, a combination of trifluridine and tipiracil, works by incorporating trifluridine into DNA, thereby inhibiting cancer cell proliferation, while tipiracil prevents trifluridine degradation, enhancing its efficacy. Irinotecan inhibits topoisomerase I, an enzyme crucial for DNA replication, leading to DNA damage and cancer cell death. Bevacizumab, an immunotherapy agent, targets vascular endothelial growth factor (VEGF), inhibiting angiogenesis, which is the formation of new blood vessels that tumors need to grow. These mechanisms are vital for colon cancer patients as they collectively disrupt cancer cell growth, enhance DNA damage, and cut off the tumor's blood supply, thereby improving treatment outcomes.