HAI + Chemotherapy +/- Bevacizumab for Liver Metastases from Colorectal Cancer

No longer recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Thrombolytics, NSAIDs, others

Disqualifiers: Brain metastases, Stroke, 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: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding bevacizumab (also known as Avastin, a type of targeted therapy) to a combination of regional and systemic chemotherapy can help prevent liver cancer recurrence after surgery. The study focuses on treating liver metastases from colorectal cancer, and participants will be randomly assigned to receive either chemotherapy alone or with bevacizumab. Suitable candidates for this trial have had colorectal cancer that spread to the liver and have undergone surgery to remove the liver tumors, with no signs of cancer elsewhere. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you have not received chemotherapy for at least 3 weeks before starting the study. Additionally, you cannot be on any investigational agents or chronic daily treatment with high-dose aspirin or certain anti-inflammatory medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research shows that the treatment using hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone, along with regular chemotherapy, is generally well-tolerated by patients. One study found that FUDR at a dose of 0.12 mg/kg/day with chemotherapy like m-FOLFOX6 was very effective in treating liver disease. Another study identified this combination as a strong option for patients with colorectal cancer that has spread to the liver.

Adding bevacizumab to HAI and regular chemotherapy has shown strong antitumor effects, effectively targeting tumors, especially in advanced cancers that have spread to the liver. While these treatments have undergone some safety checks, the complete safety profile is still under study. Patients should consult their doctors to understand what this could mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver metastases from colorectal cancer because they integrate hepatic artery infusion (HAI) with systemic chemotherapy, with or without the addition of Bevacizumab. HAI delivers chemotherapy directly to the liver, potentially enhancing drug concentration at the tumor site while minimizing systemic side effects, unlike standard treatments that distribute drugs throughout the entire body. The combination with Bevacizumab, which inhibits blood vessel growth in tumors, could further improve outcomes by starving the cancer of nutrients. This targeted approach offers hope for more effective and potentially faster responses compared to traditional systemic chemotherapy alone.

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

This trial will compare two treatment approaches for liver metastases from colorectal cancer. One group will receive hepatic arterial infusion (HAI) plus systemic chemotherapy. Studies have shown this approach can be quite effective, with patients living on average for 40 months and about 42% living for five years or more. The other group will receive bevacizumab in addition to HAI and systemic chemotherapy. Bevacizumab, a drug that helps stop tumors from growing new blood vessels, might enhance the treatment's effectiveness. Some studies suggest it can help control the disease and extend patient survival, although other research indicates that bevacizumab doesn't always prevent cancer recurrence, so results can vary. ^{6 7 8 9 10}

Who Is on the Research Team?

Nancy Kemeny, M.D

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with colorectal cancer that has spread to the liver, but not elsewhere. They must have had a liver resection and meet specific health criteria like normal blood counts and organ function tests. Pregnant women, those with recent serious injuries or surgeries, uncontrolled diseases like heart conditions or strokes, and known allergies to similar drugs are excluded.

Inclusion Criteria

Abdominal and pelvic CT scans and chest CT or x-ray within 6 weeks prior to registration (MRI of abdomen may be substituted for CT of abdomen)

Signed informed consent

My colorectal cancer has spread to my liver and there's no sign of it outside the liver.

Exclusion Criteria

I have not had radiation to the liver, but it's okay if I had pelvic radiation over 4 weeks ago.

I do not have any serious wounds, ulcers, or unhealed bone fractures.

I take more than 325 mg of aspirin daily or use anti-inflammatory drugs that affect blood clotting.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hepatic arterial infusion with floxuridine and dexamethasone, and systemic chemotherapy with or without bevacizumab

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• 5-fluorouracil
• Bevacizumab
• CPT-11
• Dexamethasone
• Floxuridine
• Leucovorin
• Oxaliplatin

Trial Overview The study aims to see if adding bevacizumab (a drug that inhibits blood vessel growth in tumors) to hepatic arterial infusion of floxuridine/dexamethasone (chemotherapy delivered directly into the liver's arteries), along with systemic chemotherapy improves disease-free survival after liver surgery.

How Is the Trial Designed?

Group I: 2 Experimental Treatment 1 Intervention

HAI plus systemic chemotherapy alone

Group II: 1 Active Control 1 Intervention

Bevacizumab in addition to HAI plus systemic chemotherapy

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4578807/

Phase II trial of hepatic artery infusional and systemic ... Overall RR was 76% (4 complete responses). Twenty-three patients (47%) achieved conversion to resection at a median of 6 months from treatment initiation.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3646323/

Randomized Phase II Trial of Adjuvant Hepatic Arterial ... This study was designed to address whether adding Bev to HAI plus systemic chemotherapy would increase recurrence-free survival (RFS) after hepatic resection.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468294222001654

Intra-arterial hepatic bevacizumab and systemic ... Concomitant IAH bevacizumab and systemic chemotherapy led to partial response in 2/10 of patients and a R0 resection of liver metastases was achieved in 1/10 ...

4. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.3557

A randomized phase II trial of adjuvant hepatic arterial ... Conclusions: The addition of bevacizumab toadjuvant HAI and systemic therapy after liver resection does not increase RFS or survival and appears to cause ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)36253-2/fulltext

Efficacy and Safety of Bevacizumab + Hepatic Arterial ... Conclusion: Bevacizumab + HAIC-FOLFIRI treatment revealed a significant disease control rate, long survival, and safety. In particular for patients with CRLM ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00200200

Study Details | NCT00200200 | Hepatic Arterial Infusion ... The purpose of this study is to determine whether the addition of bevacizumab, to hepatic arterial therapy with floxuridine (FUDR) and dexamethasone (Dex) ( ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6095333/

Hepatic arterial infusional chemotherapy in the management ... HAI with floxuridine improves survival as well as hepatic and overall disease-free survival after complete resection of CRLM, as compared with 5-FU alone.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1365182X24024237

Percutaneous hepatic artery infusion chemotherapy with ... HAIC oxaliplatin plus 5-FU/FUDR is a robust regimen for treatment-resistant CRC patients with unresectable CRLM, particularly those with liver-limited disease.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2930110/

A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in ... HAI oxaliplatin combined with systemic 5-fluorouracil, leucovorin, and bevacizumab has antitumor activity in patients with advanced cancer and liver metastases.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT00062426

Oxaliplatin and Bevacizumab (Avastin™) With Either ... PURPOSE: This randomized phase III trial is to see if oxaliplatin and bevacizumab work better when combined with either fluorouracil and leucovorin or ...