HAIP Chemotherapy for Metastatic Colorectal Cancer

Overseen By Jonathan M Hernandez, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Check-point inhibitors

Disqualifiers: Active malignancies, Uncontrolled illness, Hepatitis, 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: 8

Duration: 28-day cycles

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Many people with colorectal cancer get liver metastases. Standard treatment for this is a combination of chemotherapy drugs. Directing the chemotherapy to the liver may be effective. A device that does this a pump that delivers drugs over 2 weeks at constant rate into the hepatic artery. The person s body temperature causes the drug to flow from the pump. Researchers want to see if this helps people with colorectal metastases to the liver. Objective: To study the effectiveness of a hepatic artery infusion pump at treating colorectal metastases to the liver. Eligibility: Adults at least 18 years old with colorectal metastases to the liver Design: Participants will be screened with: Medical history Physical exam Heart, blood, and urine tests Scans Participants will stay in the hospital a few days. A small plastic tube (catheter) will be inserted in an artery into the liver. The catheter will be attached to the pump. That will lie under the skin on the abdomen. It will be small and participants will be able to feel it. Participants will get treatment in 28-day cycles. Every Day 1, they will have physical exam, symptom review, and blood tests. Every 2 weeks, they will come to the clinic to get chemotherapy by a catheter or port. Every 12 weeks, they will have a scan. Tissue samples may be taken during the study. When they finish the drug, participants may have the pump removed. They will repeat the Day 1 tests. They will be called every 6 months to see how they are doing.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents, and you should discuss your current medications with the study team to ensure they don't interfere with the trial.

What data supports the effectiveness of the drug Dexamethasone in treating metastatic colorectal cancer?

Research shows that Dexamethasone can inhibit cell growth and increase the effectiveness of chemotherapy in certain colon cancer cell lines that have a specific protein (GRα). This suggests it might help in treating colorectal cancer by making cancer cells more sensitive to chemotherapy. ^{1 2 3 4 5}

Is HAIP chemotherapy with floxuridine and dexamethasone safe for humans?

Research shows that using dexamethasone with floxuridine in HAIP chemotherapy can reduce liver-related side effects and improve treatment response in patients with liver metastases from colorectal cancer. However, there is a risk of high liver toxicity, and the treatment's safety varies depending on individual patient conditions. ^{6 7 8 9 10}

How is HAIP chemotherapy for metastatic colorectal cancer different from other treatments?

HAIP chemotherapy is unique because it delivers drugs directly into the liver's blood supply, allowing higher doses to reach the tumor with less impact on the rest of the body. The combination of floxuridine and dexamethasone in this treatment increases tumor response and reduces liver toxicity compared to floxuridine alone. ^{8 9 11 12 13}

Research Team

Jonathan M Hernandez, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults over 18 with colorectal cancer that has spread to the liver, who have tried or can't tolerate certain chemotherapy regimens. They must be in good physical condition (ECOG ≤1), have proper organ and marrow function, and agree to use contraception. Excluded are those with high-risk genetic features needing other treatments, serious illnesses, active infections like Hepatitis B/C, pregnant/nursing women, other cancers within five years (except some skin/thyroid cancers), or those eligible for complete surgical removal of liver metastases.

Inclusion Criteria

Your arteries, as seen on a special type of scan called CT angiogram, should be suitable for placing a device called HAIP (hepatic artery infusion pump).

Ability of subject to understand and the willingness to sign a written informed consent document.

HIV-positive patients may be considered for this study only after consultation with an HIV trained physician.

Exclusion Criteria

My liver cancer can be surgically removed until there's no visible disease.

You have had allergic reactions to medicines that are similar to FUDR or heparin.

My lung cancer has less than 5 large tumors, stable for 4 months, and can be surgically removed if needed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive hepatic artery infusion pump chemotherapy with floxuridine and dexamethasone in combination with systemic chemotherapy in 28-day cycles

28-day cycles

Every Day 1: physical exam, symptom review, blood tests; Every 2 weeks: clinic visit for chemotherapy; Every 12 weeks: scan

Follow-up

Participants are monitored for safety and effectiveness after treatment, including calls every 6 months

6 months

Calls every 6 months

Extension

Participants may have the pump removed and repeat Day 1 tests after finishing the drug

Treatment Details

Interventions

• Dexamethasone
• Floxuridine
• HAIP installation

Trial Overview The trial is testing a hepatic artery infusion pump delivering Floxuridine and Dexamethasone directly into the liver combined with systemic chemotherapy drugs like cetuximab and irinotecan. Participants will undergo cycles of treatment including regular exams, blood tests every two weeks for chemo via catheter/port, scans every three months, and possible tissue sampling.

Participant Groups

Group I: 1/ Arm 1 Experimental Treatment 9 Interventions

HAIP chemotherapy + 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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 515 rectal cancer patients, those who received perioperative dexamethasone had significantly lower three-year disease-free survival (62.3% vs 71.8%) and overall survival rates (74.1% vs 82.9%) compared to those who did not receive the drug.

The use of dexamethasone was independently associated with worse disease-free survival outcomes, suggesting that avoiding low-dose perioperative dexamethasone may improve survival for patients undergoing curative surgery for rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer. Yu, HC., Luo, YX., Peng, H., et al.[2021]

References

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

Correlation between glucocorticoid receptor content and the antiproliferative effect of dexamethasone in experimental solid tumors. [2013]

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

Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer. [2021]

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

Dexamethasone affects cell growth/apoptosis/chemosensitivity of colon cancer via glucocorticoid receptor α/NF-κB. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial). [2023]

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

Is dexamethasone associated with recurrence of ovarian cancer? [2014]

6. England pubmed.ncbi.nlm.nih.gov

Phase I trial of adjuvant hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone plus systemic oxaliplatin, 5-fluorouracil and leucovorin in patients with resected liver metastases from colorectal cancer. [2023]

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

A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer. [2019]

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

Hepatic artery dexamethasone infusion inhibits colorectal hepatic metastases: a regional antiangiogenic therapy. [2019]

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

Intrahepatic chemotherapy with floxuridine, leucovorin and dexamethasone in continuous infusion and mitomycin-C bolus in unresectable hepatic metastases from colorectal cancer: a phase II study. [2022]

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

Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Hepatic arterial floxuridine as second-line treatment for systemic fluorouracil-resistant colorectal liver metastases. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Hepatic arterial infusional chemotherapy in the management of colorectal cancer liver metastases. [2020]

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

Comparison of adjuvant systemic chemotherapy with or without hepatic arterial infusional chemotherapy after hepatic resection for metastatic colorectal cancer. [2022]