Hepatic Arterial Infusion + Chemotherapy for Colorectal Cancer Liver Metastases

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Oxaliplatin, Cisplatin, HAI FUDR

Disqualifiers: Radiation to liver, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to determine the safest dose for individuals who have undergone liver surgery for colorectal cancer that spread to the liver. It uses two types of chemotherapy: one that circulates throughout the body and another that targets only the liver. The goal is to assess how these drugs work together after liver surgery. Potential participants have had their liver cancer surgically removed and show no signs of cancer outside the liver. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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

Research shows that a treatment using a combination of drugs delivered directly to the liver and throughout the body may help treat liver tumors from colon cancer. This treatment includes drugs like floxuridine (FUDR) and dexamethasone, along with oxaliplatin, fluorouracil, and leucovorin. Past studies indicate that patients with liver tumors not surgically removed generally tolerated these drugs well. However, information on side effects for patients who have had part of their liver removed is still being collected.

Early results suggest that side effects are usually manageable, with common ones including nausea, tiredness, and temporary changes in liver function. Serious side effects are rare but possible. Dexamethasone is included to help protect healthy liver tissue, potentially reducing side effects from FUDR. This research continues to determine the safest doses for these drug combinations in this group of patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of hepatic arterial infusion and chemotherapy for colorectal cancer liver metastases because it introduces a unique treatment approach. Unlike standard options, which generally involve systemic chemotherapy, this method delivers floxuridine and dexamethasone directly into the liver through an implanted pump. This targeted delivery could potentially increase the treatment's effectiveness while reducing systemic side effects. Additionally, when combined with intravenous oxaliplatin and systemic fluorouracil/leucovorin, this approach aims to maximize the attack on cancer cells left after surgical removal, possibly enhancing overall outcomes.

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

This trial will evaluate the effectiveness of directly delivering medicine to the liver using drugs like floxuridine and dexamethasone, combined with whole-body chemotherapy using oxaliplatin and 5-fluorouracil, for treating liver cancer that has spread from the colon or rectum. Research has shown that this liver-focused treatment can greatly improve patient outcomes. Specifically, one study found that patients who received this treatment after surgery had an 88% chance of living for four more years and a 50% chance of their cancer not worsening during that time. These findings support the potential effectiveness of this treatment approach. ^{1 3 5 6 7}

Who Is on the Research Team?

Nancy E. Kemeny, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with colorectal cancer that has spread to the liver, but not elsewhere. They must have had surgery to remove liver disease and should have acceptable blood counts and organ function. Prior chemotherapy is okay if it was over three weeks ago, but no prior radiation to the liver or certain chemotherapies like oxaliplatin.

Inclusion Criteria

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

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)

I last received chemotherapy more than 3 weeks ago.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have an active infection, fluid in my abdomen, or brain issues due to liver disease.

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

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 intravenous oxaliplatin plus 5-fluorouracil and leucovorin as adjuvant treatment

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Floxuridine
• Fluorouracil
• Leucovorin
• Oxaliplatin

Trial Overview The study aims to find safe doses of systemic chemotherapy (OXALIPLATIN plus 5-FLUOROURACIL and LEUCOVORIN) given by vein, and regional chemotherapy (FLOXURIDINE with DEXAMETHASONE) delivered directly to the liver in patients who've had a liver resection due to metastatic colorectal cancer.

How Is the Trial Designed?

Group I: Adjuvant Hepatic Arterial Infusion & Combination Chemotherapy Experimental Treatment 8 Interventions

This is a Phase I study with the primary objective of defining the maximum tolerated dose of hepatic arterial floxuridine (FUDR) and dexamethasone (Dex) given via an implanted pump in combination with intravenous oxaliplatin plus systemic fluorouracil (5FU)/leucovorin (LV) in the adjuvant setting after resection of hepatic metastases from colorectal cancer. A total of eleven dose levels will be considered.

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

Approved in United States as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Skin cancer

Approved in European Union as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-Fluorouracil for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Medicine and Dentistry of New Jersey

Collaborator

Trials

122

Recruited

13,300+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19233901/

Phase I trial of adjuvant hepatic arterial infusion (HAI) with ... Methods: Thirty-five patients with resected liver metastases were entered into a phase I trial using HAI FUDR/Dex with escalating doses of oxal ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)40998-8/fulltext

Phase I trial of adjuvant hepatic arterial infusion (HAI) with ... With a median follow-up of 43 months, the 4-year survival and progression-free survival were 88% and 50%, respectively. Conclusions: Adjuvant therapy after ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804923007025

Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil ... Conclusion. HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM ...

4. aacrjournals.org aacrjournals.org/mct/article/8/5/1015/93410/The-role-of-floxuridine-in-metastatic-liver

The role of floxuridine in metastatic liver disease This review will put in perspective where the use of hepatic arterial infusion (HAI) with floxuridine (FUDR) fits into the therapy of liver metastases as well ...

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

A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in ... Clinical studies of HAI oxaliplatin combined with IV 5-fluorouracil (5-FU) and leucovorin have also shown encouraging results in patients with colorectal cancer ...

6. ascopubs.org ascopubs.org/doi/10.1200/jco.2005.23.16_suppl.3579

Phase I trial of hepatic arterial infusion (HAI) with ... Phase I trial of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (DEX) in combination with systemic oxaliplatin (OXAL), fluorouracil ( ...

7. 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) ( ...