Chemotherapy for Liver Cancer

Overseen By Skye C Mayo, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Must not be taking: Floxuridine, Oxaliplatin, Irinotecan

Disqualifiers: Extensive metastasis, Sclerosing cholangitis, Hepatic encephalopathy, Portal hypertension, 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: 6

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the efficacy and safety of systemic induction of mFOLFIRINOX, followed by hepatic arterial infusion (HAI) floxuridine-dexamethasone administered concurrently with systemic mFOLFIRI in treating patients with liver-dominant intrahepatic cholangiocarcinoma (ICC) that cannot be removed by surgery (unresectable). Drugs used in chemotherapy regimens, such as mFOLFIRINOX and mFOLFIRI (Oxaliplatin, Irinotecan, Fluorouracil, Folinic acid, Floxuridine) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Delivering chemotherapy via HAI (hepatic arterial infusion) can allow for liver-directed treatment while limiting toxic side effects typically seen with traditional chemotherapy.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, participants should be treatment naive, meaning they haven't had certain chemotherapy treatments before, so it's best to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the drug Irinotecan for treating liver cancer?

Irinotecan has shown strong antitumor activity in various cancers, including colorectal cancer, and has been effective in combination with other drugs. While specific data for liver cancer is not provided, its success in other cancers suggests potential benefits. ^{1 2 3 4 5}

Is irinotecan generally safe for humans?

Irinotecan has been studied extensively and is generally safe for humans, but it can cause side effects like diarrhea and leukopenia (a decrease in white blood cells). These side effects are dose-related, reversible, and vary between individuals. ^{1 3 6 7 8}

How does the drug Irinotecan differ from other treatments for liver cancer?

Irinotecan is unique because it inhibits an enzyme called topoisomerase I, which is crucial for DNA replication in cancer cells. This drug has shown a broad range of activity against various cancers and is often used in combination with other drugs to enhance its effectiveness. ^{1 3 4 9 10}

Research Team

Skye C. Mayo, MD, MPH

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

This trial is for adults with a specific liver cancer called intrahepatic cholangiocarcinoma that can't be removed by surgery. They should not have had previous chemotherapy, must have good blood counts and organ function, and agree to use birth control. People with certain other health conditions or who've had many abdominal surgeries are excluded.

Inclusion Criteria

My kidney function, measured by creatinine levels or clearance, is within the required range.

White blood cell (WBC) >= 3000 cells/mm^3

My liver cancer cannot be removed with surgery.

Exclusion Criteria

I have a blockage in my bile duct that needed a stent.

The doctor believes that you have less than 12 weeks to live.

I have been treated with floxuridine, oxaliplatin, or irinotecan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Systemic induction of mFOLFIRINOX for 4 cycles with a 25% dose reduction of oxaliplatin, irinotecan, and fluorouracil

8 weeks

Every 2 weeks for 4 cycles

Treatment Period 2

HAI delivery of floxuridine-dexamethasone with concurrent systemic mFOLFIRI for 2 cycles

8 weeks

Every 4 weeks for 2 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Dexamethasone
• Floxuridine
• Irinotecan
• Oxaliplatin

Trial Overview The study tests mFOLFIRINOX followed by hepatic arterial infusion of floxuridine-dexamethasone alongside systemic mFOLFIRI. It aims to see if targeting the liver directly with these drugs helps more than standard treatment while reducing side effects.

Participant Groups

Group I: mFOLFIRINOX, Floxuridine-DEX, mFOLFIRI Experimental Treatment 7 Interventions

Treatment Period 1 - mFOLFIRINOX for 4 cycles (cycle = 14 days) Cycle 1 * Oxaliplatin 85 mg/m2 intravenously (iv) over 2 hours * Folinic acid 400 mg/m2 iv over 2 hours * Irinotecan 165 mg/m2 iv over 90 minutes * Fluorouracil 400 mg/m2 iv bolus after folinic acid * Fluorouracil 2,400 mg/m2 continuous infusion over 46 hours Dosages on Cycle 2, 3, and 4 will be reduced by 25% Treatment Period 2 - HAI delivery of floxuridine + mFOLFIRI for 2 cycles (cycle = 28 days) * Floxuridine-DEX (with heparin and saline) - 0.12 mg/kg/day; via HAI pump, adjusted for weight and flow rate mFOLFIRI on Day 15 * Irinotecan 180 mg/m2 iv over 30 minutes to 1 hour * Folinic acid 400mg/m2 iv over 30 minutes to 1 hour * 5-FU 1000 mg/m2 continuous infusion over 46 hours

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

Approved in United States as Camptosar for:

• Colorectal cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer

Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

Approved in Canada as Irinotecan for:

• Colorectal cancer

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

Irinotecan is an approved treatment for colorectal cancer that does not respond to fluorouracil, highlighting its role in managing difficult cases of this disease.

The review addresses the drug's toxicity and management strategies, indicating that while irinotecan is effective, careful monitoring and handling of side effects are crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Use of Irinotecan: Current Status and Future Considerations. Saltz, LB.[2019]

Combining irinotecan hydrochloride (SN-38) with cisplatin significantly enhances the anticancer effects against colorectal cancer, as shown by a study using freshly isolated cancer cells from 20 patients.

The study found that even at lower concentrations, the combination of SN-38 and cisplatin produced a strong synergistic effect, suggesting a promising strategy for improving chemotherapy outcomes in advanced colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. Tsunoda, T., Tanimura, H., Hotta, T., et al.[2019]

CPT-11 (irinotecan) is an effective anticancer drug that inhibits DNA topoisomerase 1 and has shown activity against solid tumors, including those resistant to other treatments, based on results from three European phase I trials.

The optimal dosage schedule for CPT-11 was determined to be 350 mg/m2 administered as an intravenous infusion once every 3 weeks, as it provided the highest dose intensity with manageable toxicity, particularly with the use of high-dose loperamide for diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for phase II studies, as determined by European phase I studies. Armand, JP., Extra, YM., Catimel, G., et al.[2020]

References

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

Clinical Use of Irinotecan: Current Status and Future Considerations. [2019]

2. Japan pubmed.ncbi.nlm.nih.gov

[Standard therapy of CPT-11 for colorectal cancer]. [2018]

3. Japan pubmed.ncbi.nlm.nih.gov

[CPT-11 (irinotecan)--evidence from molecular and pharmacological studies and clinical applications]. [2018]

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

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

CPT-11 (irinotecan) in the treatment of colorectal cancer. [2019]

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

Phase I and pharmacokinetic study of the camptothecin derivative irinotecan, administered on a weekly schedule in cancer patients. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Activity of CPT-11 (irinotecan hydrochloride), a topoisomerase I inhibitor, against human tumor colony-forming units. [2019]

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

Phase II study of irinotecan as first-line chemotherapy for patients with advanced colorectal carcinoma. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Rationale for the dosage and schedule of CPT-11 (irinotecan) selected for phase II studies, as determined by European phase I studies. [2020]

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

In vitro sensitivity of fresh ovarian carcinoma specimens to CPT-11 (irinotecan). [2018]