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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new chemotherapy approach for liver cancer, specifically intrahepatic cholangiocarcinoma (ICC) that cannot be surgically removed. The trial aims to determine if combining two chemotherapy regimens, with one delivered directly to the liver, can effectively stop the cancer from growing or spreading. This method might limit the typical side effects of chemotherapy. The trial suits individuals diagnosed with ICC that cannot be surgically removed and who have not received certain chemotherapy treatments before. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important research.

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.

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

Research has shown that the mFOLFIRINOX chemotherapy treatment, which includes drugs like oxaliplatin and irinotecan, is generally well-tolerated. One study found this combination safe for patients with serious liver problems caused by cancer spread, suggesting that mFOLFIRINOX might also be safe for other liver conditions.

For the hepatic arterial infusion (HAI) treatment using floxuridine and dexamethasone, studies have reported some side effects, such as liver issues and higher bilirubin levels (a substance made by the liver). However, most patients managed these side effects. Another study confirmed that this treatment could be safely combined with other chemotherapy.

While both treatments have shown some side effects, they have generally been well-tolerated in past studies. It is important to note that this trial is in Phase 2, meaning the treatment has shown some safety in earlier tests but is still being evaluated for effectiveness and safety in a larger group. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for liver cancer because they combine innovative chemotherapy regimens with a unique delivery method. Unlike standard treatments that typically rely on systemic chemotherapy, this approach includes hepatic arterial infusion (HAI) to directly deliver floxuridine to the liver, potentially increasing the drug's effectiveness while reducing systemic side effects. Additionally, the combination of mFOLFIRINOX and mFOLFIRI regimens incorporates both irinotecan and oxaliplatin, aiming to enhance the overall cancer-fighting capability. This multi-pronged strategy could offer new hope for patients by targeting liver tumors more precisely and aggressively than traditional chemotherapy alone.

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

Research has shown that mFOLFIRINOX, one of the treatment options in this trial, can be quite effective for some liver cancer patients. In one study, about 71% of patients responded well, living longer and experiencing slower disease progression. Another treatment option in this trial, mFOLFIRI, demonstrated a response rate of 56% in different studies. For floxuridine given directly to the liver (HAI), also under study in this trial, research suggests it works well for advanced liver cancer, especially when surgery isn't an option. These treatments target cancer cells by either killing them or stopping their growth. Overall, promising evidence indicates that these drugs can help treat liver cancer. ^{2 3 4 6 7}

Who Is on the Research Team?

Skye C. Mayo, MD, MPH

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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

I have treated hepatitis and my liver functions well.

Exclusion Criteria

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3396196/

Efficacy of hepatic arterial infusion chemotherapy in ... CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00410956?cond=%22Adult%20Hepatocellular%20Carcinoma%22&intr=%22Gastrointestinal%20Agents%22&viewType=Table&rank=3

Floxuridine and Dexamethasone as a Hepatic Arterial Infusion ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)40439-0/fulltext

Regional chemotherapy for unresectable primary liver cancer This study reports the results of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (dex) in patients with unresectable intrahepatic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3123741/

Treating Primary Liver Cancer with Hepatic Arterial Infusion ... This study investigated the efficacy and safety of adding systemic (IV) bevacizumab (Bev) to hepatic arterial infusion (HAI) with floxuridine ( ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0923753419404390

results of a phase II clinical trial and assessment of DCE- ... This study reports the results of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (dex) in patients with unresectable intrahepatic ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16028279/

Hepatic arterial infusion of floxuridine and dexamethasone ... The major toxicities were liver bilomas (7.9%), elevation in bilirubin level >3 (22%), and biliary sclerosis (9.5%). Hematologic and gastrointestinal toxicity ...

7. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2001.19.10.2687

Phase I Study of Hepatic Arterial Infusion of Floxuridine ... CONCLUSION: Combination therapy with HAI FUDR and dexamethasone plus systemic irinotecan may be safely administered to patients with unresectable hepatic ...