5FU/LV + Regorafenib for Colorectal Cancer

Overseen By Safiya Joseph

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must not be taking: Corticosteroids, Immunosuppressants, Antivirals, others

Disqualifiers: Cardiac issues, Uncontrolled hypertension, Active infection, 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

Compensation: Varies

Number of Visits: 1

Duration: 24-48 weeks

57 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to evaluate their effectiveness and safety for individuals with metastatic colorectal cancer previously treated with two other therapies. It compares two drug combinations: one group receives 5FU/LV (a chemotherapy regimen) with regorafenib (a targeted therapy), while the other receives trifluridine-tipiracil plus bevacizumab. The study seeks participants with metastatic colorectal cancer who have not responded to previous treatments and have at least one measurable tumor. Participants should also have a life expectancy of at least six months and be able to swallow oral medications. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain treatments like corticosteroids or have recently received other investigational agents, you may not be eligible. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is investigating the safety of combining two drugs, 5FU/LV and regorafenib, to treat metastatic colorectal cancer. This combination might be an option for patients whose cancer has not responded to other treatments. Some studies have focused on patient tolerance to this treatment.

Past trials have examined how patients cope with side effects, particularly regarding safety. Common side effects of regorafenib include fatigue, redness and swelling on the hands and feet, and diarrhea. The combination with 5FU/LV has been used before, and patients have generally managed these side effects.

As this trial is in an early stage, researchers are closely monitoring the treatment's safety, paying special attention to any side effects that might occur. Prospective participants should discuss potential risks and benefits with their healthcare provider to determine if this trial is suitable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for colorectal cancer because they combine well-established chemotherapy agents with cutting-edge targeted therapy. The combination of 5FU/LV with regorafenib is unique because regorafenib is a multi-kinase inhibitor that can target multiple pathways involved in tumor growth and angiogenesis, potentially enhancing the effectiveness of traditional chemotherapy. This dual-action approach might offer better control over cancer progression compared to standard treatments, which often rely on chemotherapy alone. Additionally, the use of FTD-TPI plus bevacizumab as an active comparator brings another layer of innovation, as bevacizumab targets the blood vessels that supply tumors, potentially improving outcomes. These novel combinations give hope for more effective management of colorectal cancer, especially in cases where the disease has become resistant to conventional therapies.

What evidence suggests that this trial's treatments could be effective for metastatic colorectal cancer?

This trial will evaluate the combination of two drugs, 5FU/LV and regorafenib, as a promising treatment for advanced colorectal cancer. Participants will receive this combination, which research indicates can extend survival, with many living at least 12 months. This combination targets cancer cells more effectively, potentially slowing the disease. Overall, this approach could offer a new option for patients who haven't found success with other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Maen Abdelrahim, MD, PhD, Pharm D

Principal Investigator

The Methodist Hospital Research Institute

Abdullah Esmail, MD

Principal Investigator

Houston Methodist Neal Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with metastatic colorectal cancer who are undergoing their third round of treatment. Participants must be eligible for the third-line setting and able to take oral medication, as well as receive intravenous treatments.

Inclusion Criteria

My colorectal cancer has spread and this was confirmed by a lab test.

Subjects must be able to understand and be willing to sign the written informed consent form

A minimum of one measurable disease per RECISTv1.1

Exclusion Criteria

Hepatic laboratory values exceeding specified limits

Clinically significant laboratory abnormalities that would compromise patient safety or the outcome of the study

I have serious heart problems that are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5FU/LV in combination with regorafenib or FTD-TPI plus bevacizumab until disease progression or unacceptable toxicity, up to 12 cycles

24-48 weeks

Bi-weekly visits for Arm 1, monthly visits for Arm 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

What Are the Treatments Tested in This Trial?

Interventions

• 5FU/LV
• Regorafenib

Trial Overview The study compares two treatments: one combines chemotherapy (5FU/LV) with regorafenib, while the other uses trifluridine-tipiracil (FTD-TPI) plus bevacizumab. Patients will be randomly assigned to either group and treated in cycles up to 12 times or until disease progression.

How Is the Trial Designed?

Group I: 5FU/LV in combination with regorafenib Experimental Treatment 2 Interventions

5FU/LV will be administered to 38 patients as (LV \[400 mg/m² IV over 120 minutes\], followed by 5FU \[400 mg/m² IV bolus then 2400 mg/m² IV infusion over 46 hours\] in 2-week cycles) and regorafenib will be administered dose of 80-120 mg per day with weekly 40 mg per day increases to a maximum of 120 mg per day for 3 weeks on /1 week off until disease progression, up to 12 cycles of treatment.

Group II: trifluridine-tipiracil (FTD-TPI) plus bevacizumab Active Control 2 Interventions

an additional 19 patients, will be given as FTD-TPI, administered orally, trice daily, at a starting dose of 35 mg/m2 of body-surface area, on days 1 through 5 and on days 8 through 12 every 28 days. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered intravenously on days 1 and 15. The 28-day treatment cycle continued until disease progression or unacceptable toxic effects occurred or consent was withdrawn, up to 12 cycles of treatment.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Regorafenib is an oral multi-kinase inhibitor that has shown significant survival benefits in metastatic colorectal cancer and has been FDA approved for this use since 2012.

The drug also improves progression-free survival in patients with metastatic gastrointestinal stromal tumors and advanced hepatocellular carcinoma, leading to its FDA approval for these conditions as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2018]

In a study of 43 patients aged 70 and older with metastatic colorectal cancer, regorafenib showed a disease control rate of 31.4% after 2 months, indicating it can be an effective treatment option for older patients who have failed previous therapies.

However, the treatment was associated with significant toxicities, with 35 out of 42 patients experiencing grade 3-4 adverse events, particularly fatigue, hypertension, and hand-foot skin reactions, suggesting that careful monitoring is needed, especially for patients over 80 or with impaired autonomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD. Aparicio, T., Darut-Jouve, A., Khemissa Akouz, F., et al.[2021]

Regorafenib is an FDA-approved oral medication that targets multiple kinases involved in cancer growth and has shown survival benefits in patients with metastatic colorectal cancer after standard treatments have failed.

In addition to colorectal cancer, regorafenib significantly improves progression-free survival in patients with metastatic gastrointestinal stromal tumors (GIST) and is currently being tested in various other cancers, including renal cell carcinoma and hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2015]

In a study involving 181 patients with metastatic colorectal cancer, the combination of regorafenib and FOLFIRI resulted in a modest increase in progression-free survival (PFS) compared to FOLFIRI alone, with a median PFS of 6.1 months versus 5.3 months.

While the addition of regorafenib improved the response rate (34% vs 21%), it did not significantly extend overall survival, and patients experienced increased rates of serious side effects such as diarrhea and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, randomized, double-blind phase 2 trial of FOLFIRI with regorafenib or placebo as second-line therapy for metastatic colorectal cancer. Sanoff, HK., Goldberg, RM., Ivanova, A., et al.[2019]

Regorafenib, a multikinase inhibitor used for advanced solid tumors, was associated with a range of adverse events (AEs) in a meta-analysis of 2,065 patients, with the most common being hand-foot skin reaction (54%), diarrhea (33%), and fatigue (32%).

The analysis revealed that regorafenib significantly increases the risk of developing AEs compared to placebo, highlighting the importance of monitoring these effects to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events risk associated with regorafenib in the treatment of advanced solid tumors: meta-analysis of randomized controlled trials. Yin, X., Yin, Y., Shen, C., et al.[2022]

Regorafenib is an effective treatment for patients with metastatic colorectal cancer who have previously undergone multiple chemotherapy regimens, showing a significant improvement in overall survival compared to placebo (6.4 months vs 4 months).

The treatment is associated with manageable side effects, with the most common severe adverse events being hand-foot syndrome (17%) and asthenia (10%), indicating that while it is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Regorafenib approved in Metastatic Colorectal cancer]. André, T., Dumont, SN.[2022]

Regorafenib is the first approved tyrosine kinase inhibitor for metastatic colorectal cancer, showing significant improvements in progression-free and overall survival in patients who had previously undergone multiple lines of chemotherapy and targeted therapies, based on results from two phase III trials.

While regorafenib has a safety profile similar to other tyrosine kinase inhibitors, it is associated with specific adverse events like hand-foot skin reaction and hypertension, which can be managed effectively through patient education and timely dose adjustments, allowing patients to continue benefiting from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving patient outcomes with regorafenib for metastatic colorectal cancer - patient selection, dosing, patient education, prophylaxis, and management of adverse events. Hofheinz, RD., Arnold, D., Kubicka, S., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06887218

NCT06887218 | 5-Fluorouracil/Leucovorin (5FU/LV) in ... Overall survival rate of patients with metastatic colorectal cancer treated with 5FU/LV in combination with regorafenib at 12 months. From date of initial ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/584881

5-Fluorouracil/Leucovorin (5FU/LV) in Combination With ... Outcome Measures​​ Overall survival rate of patients with metastatic colorectal cancer treated with 5FU/LV in combination with regorafenib at 12 months.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12109328/

Safety and Efficacy of Regorafenib and 5-Fluorouracil ... This study highlights that using a combination of regorafenib plus 5-FU can be a potential treatment option for patients with refractory mCRC.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.140

A phase I dose-escalation study of an all-in-one 5 ... Conclusions: Deflexifol is safe and well tolerated at doses of 5-FU up to 40% higher than typically administered by the standard modified de ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT06887218

5-Fluorouracil/Leucovorin (5FU/LV) in Combination With ... Overall survival rate of patients with metastatic colorectal cancer treated with 5FU/LV in combination with regorafenib at 12 months. From date of initial ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03099486

Regorafenib Plus 5-Fluorouracil/Leucovorin Beyond ... This is a single arm open label pilot phase II trial of Regorafenib PO plus 5-FU/LV infusion in 15 mCRC patients who progressed on prior Regorafenib ...