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

Trial Summary

What is the purpose of this trial?

Most patients with mCRC are treated with palliative chemotherapy and only a small number of patients with limited metastatic disease achieve long-term remission following metastasectomy. There is a growing need for more effective treatment in patients with liver-only mCRC to improve the rate of curative resection without compromising QOL.The current study is informed by our patient's needs. It aims to evaluate the rate of conversion therapy in patients with unresectable liver-only mCRC using the combination of FOLFOXIRI and bevacizumab and to assess the association between an early FDG-PT/CT response and other clinical and pathological biomarkers and hepatic metastasectomy.

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.

What data supports the effectiveness of the drug FOLFOXIRI + Bevacizumab for colorectal cancer?

Research shows that FOLFOXIRI combined with bevacizumab is effective as a first-line treatment for metastatic colorectal cancer, with studies indicating it improves treatment outcomes compared to other regimens. Bevacizumab, when added to chemotherapy, has been shown to increase the effectiveness of the treatment in various studies. ^{1 2 3 4 5}

Is FOLFOXIRI plus Bevacizumab safe for humans?

FOLFOXIRI plus Bevacizumab has been used in treating metastatic colorectal cancer, but it can lead to significant side effects like neutropenia (low white blood cell count), fatigue, neuropathy (nerve damage), and hypertension (high blood pressure). While it shows promise in improving survival, it is important to manage these side effects carefully to avoid treatment interruptions. ^{5 6 7 8 9}

How is the drug FOLFOXIRI + Bevacizumab different from other treatments for colorectal cancer?

FOLFOXIRI plus Bevacizumab is unique because it combines a powerful chemotherapy regimen (FOLFOXIRI) with Bevacizumab, a drug that targets blood vessel growth in tumors, offering improved survival rates for patients with metastatic colorectal cancer compared to some other treatment combinations. ^{2 4 5 6 10}

Research Team

Shahid Ahmed, MD, PhD

Principal Investigator

University of Saskatchewan

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer. [2021]

2. England pubmed.ncbi.nlm.nih.gov

FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of FOLFOXIRI plus molecular target drug therapy for metastatic colorectal cancer: A multicenter retrospective study. [2022]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Bevacizumab plus FOLFIRI or FOLFOX as third-line or later treatment in patients with metastatic colorectal cancer after failure of 5-fluorouracil, irinotecan, and oxaliplatin: a retrospective analysis. [2021]

6. United States 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. [2022]

7. Switzerland 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. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

[Comparative Safety Assessment of Ramucirumab plus FOLFIRI and Bevacizumab plus FOLFIRI in Second- and Later-Line Treatment in Japanese Patients with Metastatic Colorectal Carcinoma]. [2023]

9. France pubmed.ncbi.nlm.nih.gov

A Review of Clinical Studies and Practical Guide for the Administration of Triplet Chemotherapy Regimens with Bevacizumab in First-line Metastatic Colorectal Cancer. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer. [2021]