FOLFOXIRI + Bevacizumab for Colorectal Cancer

(CONVERSION Trial)

Overseen By Michael Moser

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Saskatchewan

Must be taking: FOLFOXIRI, Bevacizumab

Disqualifiers: Pregnancy, Active cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

Duration: 24 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments called FOLFOXIRI (a chemotherapy regimen) and bevacizumab (a targeted therapy) for individuals with colorectal cancer that has spread only to the liver and cannot be surgically removed. The goal is to determine if these treatments can shrink the cancer enough to make surgery possible in the future. The trial seeks participants diagnosed with this specific type of colorectal cancer who have not received chemotherapy for advanced disease and have healthy bone marrow, liver, and kidneys. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using FOLFOXIRI with bevacizumab is generally safe for patients with advanced colorectal cancer. Earlier studies found that this combination can extend patients' lives. Although some side effects were reported, they were usually manageable and similar to those from other cancer treatments. This treatment is often used as a standard option, indicating it is fairly well-tolerated. As with any treatment, side effects can vary, so discussing them with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

FOLFOXIRI combined with Bevacizumab is unique because it targets colorectal cancer with a powerful one-two punch. Unlike standard treatments that typically involve a single chemotherapy regimen, FOLFOXIRI is a cocktail of three chemotherapies: 5-fluorouracil, leucovorin, and irinotecan. This combination is designed to attack cancer cells on multiple fronts. Adding Bevacizumab, which inhibits the growth of blood vessels that feed tumors, could enhance this effect, potentially leading to better outcomes. Researchers are excited about this approach as it may offer improved effectiveness and a new hope for patients with advanced colorectal cancer.

What evidence suggests that FOLFOXIRI and Bevacizumab might be an effective treatment for colorectal cancer?

Studies have shown that combining FOLFOXIRI and bevacizumab can effectively treat metastatic colorectal cancer (mCRC). Research indicates that this treatment helps patients live longer without cancer progression. In one study, patients lived an average of 12.8 months without cancer progression, and their overall survival was 27.9 months. This is promising for those battling mCRC. Additionally, this treatment combination may benefit patients with limited options, suggesting that FOLFOXIRI and bevacizumab could offer hope for better outcomes in mCRC. ^{1 2 6 7 8}

Who Is on the Research Team?

Shahid Ahmed, MD, PhD

Principal Investigator

University of Saskatchewan

Are You a Good Fit for This Trial?

Adults aged 18-70 with a specific type of colon or rectum cancer that has spread to the liver but not beyond, who haven't had chemo for advanced disease and are in good health otherwise. They should be able to perform daily activities with ease or have only slight limitations.

Inclusion Criteria

I am fully active or able to carry out light work.

I haven't had chemotherapy for my advanced disease.

My bone marrow, liver, and kidneys are working well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FOLFOXIRI and Bevacizumab every two weeks for a total of 12 cycles

24 weeks

12 visits (in-person)

Assessment

Reassessment of liver metastases resectability by a multidisciplinary team

4 weeks

Follow-up

Participants are monitored for safety, effectiveness, and progression-free survival

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• FOLFOXIRI and Bevacizumab

Trial Overview The trial is testing a combination of drugs (FOLFOXIRI and Bevacizumab) on patients whose colorectal cancer has spread just to the liver, aiming to shrink tumors enough so surgery might remove them. The study also looks at how early responses predict success.

How Is the Trial Designed?

Group I: Single arm Experimental Treatment 1 Intervention

FOLFOXIRI and Bevacizumab

Who Is Running the Clinical Trial?

University of Saskatchewan

Lead Sponsor

Trials

261

Recruited

156,000+

Published Research Related to This Trial

The combination of FOLFOXIRI and bevacizumab demonstrated a promising progression-free survival (PFS) rate of 74% at 10 months in patients with unresectable metastatic colorectal cancer, based on a phase 2 study involving 57 patients.

The treatment was found to be safe, with no unexpected adverse events reported, although common serious side effects included neutropenia and hypertension, indicating that while effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as first-line treatment for metastatic colorectal cancer: a phase 2 trial. Masi, G., Loupakis, F., Salvatore, L., et al.[2022]

In patients with unresectable RAS wild-type metastatic colorectal cancer, first-line bevacizumab-based chemotherapy significantly reduces the risk of dermatological and renal adverse events, but increases the risk of cardiovascular issues like hypertension and arrhythmia.

Conversely, cetuximab-based chemotherapy is associated with a higher incidence of dermatological and renal adverse events, particularly rashes and electrolyte disorders, highlighting the need for careful selection of targeted therapies based on safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability on Serious Adverse Events of First-Line Bevacizumab and Cetuximab for RAS Wild-Type Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Han, YN., Choi, YJ., Rhie, SJ.[2022]

In a study of 69 Asian patients with metastatic colorectal cancer, the combination of FOLFOXIRI and bevacizumab resulted in a high progression-free survival (PFS) rate of 75.2% at 10 months, indicating its effectiveness as a first-line treatment.

However, this regimen was associated with significant adverse events, particularly high rates of neutropenia (72.5%) and hypertension (34.8%), highlighting the need for careful monitoring, especially in patients with specific UGT1A1 genetic polymorphisms that increase the risk of severe neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study. Oki, E., Kato, T., Bando, H., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39196470/

Real-world outcomes of FOLFOXIRI plus bevacizumab in ... The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6-15.0) and 27.9 months (95% CI 21.6-34.2), respectively. The objective ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1403108

Initial Therapy with FOLFOXIRI and Bevacizumab for ... This phase 3, randomized study showed improved progression-free survival among patients with metastatic colorectal cancer after treatment with ...

3. nature.com nature.com/articles/s41416-023-02496-4

Efficacy and quality of life for FOLFOX/bevacizumab + FOLFOXIRI plus bevacizumab has demonstrated benefits for metastatic colorectal cancer (mCRC) patients. However, challenges arise in its ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT00719797

Study Details | NCT00719797 | Combination ... This randomized phase III trial is comparing two combination chemotherapy regimens given together with bevacizumab to see how well they work as first-line ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925002515

The relative dose intensity of first-line FOLFOXIRI and ... Overall, 282/581 (49 %) and 404/580 (70 %) of patients treated with FOLFOXIRI/bev and doublets/bev, respectively, received RDI≥ 80 %. Patients receiving RDI≥ 80 ...

6. esmoopen.com esmoopen.com/article/S2059-7029(23)00103-5/fulltext

FOLFOXIRI plus bevacizumab as standard of care for first- ... FOLFOXIRI plus Bev showed a significant prolongation of PFS from 9.7 months in FOLFIRI plus Bev to 12.1 months [hazard ratio (HR) 0.75; P = ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666634024002162

QUATTRO-II randomized trial: CAPOXIRI+bevacizumab vs. ... The study aimed to assess the efficacy and safety of CAPOXIRI+BEV vs. FOLFOXIRI+BEV in mCRC. This study evaluated the efficacy and safety of ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.198

A multicenter phase II study (SYLT-026). Cadonilimab in combination with FOLFOXIRI and Bevacizumab demonstrated promising efficacy and a manageable safety profile as a first-line treatment for ...