M9241 + HAIP Chemotherapy for Liver Cancers

Overseen By Cathleen E Hannah, C.R.N.P.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, rIL-12

Disqualifiers: Autoimmune diseases, Organ transplant, Cardiovascular disease, 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: 4

Duration: Until disease progression or unacceptable toxicity

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for liver cancer by combining a unique drug, PDS01ADC, with a method that delivers chemotherapy directly to the liver using the Intera 3000 Hepatic Artery Infusion Pump (HAIP). The goal is to determine if this combination can enhance the immune system's ability to fight cancer. The study involves patients with bile duct cancer confined to the liver or colorectal cancer that has spread to the liver. Participants should have previously undergone chemotherapy and have liver cancer that cannot be surgically removed. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to the development of potentially effective therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking other investigational drugs or have previously received certain treatments like rIL-12.

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

Research has shown that the M9241 drug, also known as NHS-IL12, is generally well-tolerated. For example, one study combining M9241 with another drug found that patients could handle it well, with side effects not being too severe. Another study indicated that M9241 had a safe profile when administered every two weeks, suggesting it is safe for long-term use.

The Intera 3000 Hepatic Artery Infusion Pump (HAIP) is an FDA-approved device that delivers chemotherapy drugs directly to the liver. This method is already used to treat certain liver cancers and is designed to reduce side effects by targeting the tumor directly, rather than affecting the whole body.

Overall, these findings suggest that both M9241 and the Intera 3000 HAIP are considered safe, with manageable side effects, based on previous studies and their current use in treating other conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine a novel immunotherapy agent, M9241, with the precise delivery of chemotherapy directly to the liver via the Intera 3000 Hepatic Artery Infusion Pump (HAIP). Unlike current standard treatments like systemic chemotherapy, which affects the entire body, HAIP delivers high concentrations of chemotherapy directly to the liver, potentially reducing systemic side effects. Additionally, M9241 is an innovative treatment that aims to boost the immune system's ability to fight cancer, offering a new mechanism of action. This combination has the potential to enhance treatment effectiveness specifically for liver cancers, making it a promising option for patients with this challenging condition.

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

Research has shown that using a hepatic artery infusion pump (HAIP) with chemotherapy effectively treats liver cancer. Studies indicate that HAIP therapy can extend patients' lives and control liver tumors. One study found that individuals receiving HAIP with regular chemotherapy lived for a median of 32.8 months. In this trial, one arm will combine HAIP with PDS01ADC and either FOLFOX or FOLFIRI chemotherapy regimens. Another arm will combine HAIP with PDS01ADC and the GemOx regimen. Early trials suggest that the immunotherapy drug PDS01ADC can help the immune system fight cancer cells. This drug targets tumor areas, potentially making cancer treatment more effective. Together, these treatments offer a promising approach for certain types of liver cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Jonathan M Hernandez, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with bile duct cancer confined to the liver or colorectal cancer that has spread to the liver. They must be able to handle chemotherapy, agree to use effective contraception, and not breastfeed if applicable. HIV-positive individuals can join if their viral load is undetectable.

Inclusion Criteria

Subjects must agree to co-enroll on the Surgical Oncology Program s tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors

I can undergo chemotherapy with specific drugs for my colorectal or intrahepatic cholangiocarcinoma.

Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP)

Exclusion Criteria

I am on steroids for hormone replacement, not exceeding 10 mg of prednisone or its equivalent daily.

I have not had a stroke, heart attack, severe heart failure, or serious heart rhythm problems in the last 6 months.

I have an active Hepatitis B or C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive HAIP chemotherapy with PDS01ADC and systemic therapy until disease progression or unacceptable toxicity

Until disease progression or unacceptable toxicity

2 visits per month (in-person), CT scans every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month after treatment ends, then every 6 months for 5 years

1 follow-up visit (in-person), then contact every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil
• Dexamethasone
• Floxuridine
• Gemcitabine
• Intera 3000 Hepatic Artery Infusion Pump (HAIP)
• Irinotecan
• Leucovorin
• M9241
• Oxaliplatin

Trial Overview

The trial tests M9241 combined with HAIP-delivered chemo (Floxuridine) and systemic therapy (5-Fluorouracil, Oxaliplatin, Leucovorin for colorectal; Gemcitabine for bile duct). Participants will receive treatments biweekly until disease progression or unacceptable side effects occur.

How Is the Trial Designed?

Group I: 2/HAIP +PDS01ADC+GemOx Experimental Treatment 9 Interventions

PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with GemOx

Group II: 1/ HAIP +PDS01ADC+FOLFOX or FOLFORI Experimental Treatment 8 Interventions

PDS01ADC+HAIP FUDR and Dexamethasone chemotherapy in combination with FOLFOX or FOLFIRI

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The use of hepatic artery infusion pumps (HAIPs) for chemotherapy has seen a resurgence since the 1960s, primarily for treating liver metastases that cannot be surgically removed, although earlier use was limited due to complications and minimal survival benefits.

This study conducted a systematic literature review, narrowing down 511 initial titles to 45 relevant publications, highlighting the need for better nursing care guidelines for patients with HAIPs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatic artery infusion pump in the treatment of liver metastases. Parks, L., Routt, M.[2018]

Robotic hepatic artery infusion pump (HAIP) placement is a safe and minimally invasive procedure that significantly reduces the likelihood of needing to convert to an open surgery compared to laparoscopic placement (17% vs. 67%).

There is a trend indicating that robotic HAIP placement may lead to a shorter hospital stay (4 days) compared to both open and laparoscopic placements (5 days each), although this finding was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robotic hepatic arterial infusion pump placement. Qadan, M., D'Angelica, MI., Kemeny, NE., et al.[2018]

In a study of 25 patients with chemotherapy-resistant colorectal liver metastases, hepatic artery infusion pump (HAIP) therapy resulted in a partial response in 40% of cases, indicating its potential efficacy in this challenging patient population.

Patients with isolated colorectal liver metastases had a median overall survival of 14 months compared to 8 months for those with extrahepatic disease, suggesting that HAIP may be more beneficial for patients with localized liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage regional therapy using hepatic artery infusion pump in unresectable chemotherapy resistant colorectal liver metastases. O'Leary, MP., Wang, C., Sandhu, J., et al.[2022]

In a study of 467 patients, the placement of a hepatic artery infusion pump (HAIP) during concurrent hepatic and colorectal surgeries did not increase the risk of serious morbidity or death compared to surgeries without HAIP placement.

However, HAIP placement was associated with longer operative times and increased length of hospital stay, indicating that while it is safe, it may require more resources and time during recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Risk of Performing Concurrent Procedures with Hepatic Artery Infusion Pump Placement. Brajcich, BC., Bentrem, DJ., Yang, AD., et al.[2021]

A multicenter study involving 154 patients demonstrated that hepatic artery infusion pump (HAIP) chemotherapy can be safely implemented at various centers, with only 4.6% experiencing major complications during hospitalization.

The treatment showed promising efficacy, with 56.5% of patients achieving a complete or partial response and 7.8% undergoing curative liver resection, indicating that HAIP is a viable option for managing unresectable colorectal liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study. Muaddi, H., D'Angelica, M., Wiseman, JT., et al.[2022]

Citations

1.

interaoncology.com

interaoncology.com/healthcare-professionals/clinical-evidence/colorectal-cancer-liver-metastases/hepatic-arterial-infusion-in-combination-with-modern-systemic-chemotherapy

Clinical Evidence

Patients treated with the Intera 3000 HAI Pump with floxuridine, and systemic chemotherapy had a median overall survival of 32.8 months.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05286814

NCT05286814 | PDS01ADC in Combination With Hepatic ...

To see if treatment with HAIPs to deliver liver-directed chemotherapy in combination with PDS01ADC is effective for certain cancers. Eligibility: People aged 18 ...

3.

colorectalcancer.org

colorectalcancer.org/treatment/types-treatment/chemo-radiation-and-other-therapies/hepatic-artery-infusion-hai-therapy

Hepatic Artery Infusion (HAI) Therapy

Clinical studies have shown that HAI therapy may reduce the size of tumors in the liver, improve disease control in the liver, increase chances of liver ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6863781/

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy ...

The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11108096/

Current practices in hepatic artery infusion (HAI) ...

Currently, the PUMP Trial is a randomized clinical trial investigating adjuvant HAI chemotherapy after resection of CRLM in patients with a low clinical risk ...

6.

interaoncology.com

interaoncology.com/patients-caregivers/hai-therapy/safety-information

Intera 3000 HAI Pump Safety Information for Patients

Safety information for Healthcare Professionals about the Intera 3000 Hepatic Artery Infusion Pump.

7.

interaoncology.com

interaoncology.com/patients-caregivers/intera-3000-hai-pump

Intera 3000 HAI Pump

The Intera 3000 HAI Pump is the only FDA-approved implantable pump for HAI therapy. The Intera 3000 HAI Pump contains a drug reservoir which is attached to a ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8749357/

Safety and Feasibility of Initiating a Hepatic Artery Infusion ...

Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM).

9.

interaoncology.com

interaoncology.com/downloads/intera-3000-pump/ifun-0883-20072-intera-3000-hai-pump-ifu-rev-c.pdf

intera 3000 hepatic artery infusion pump

The pump contains a safety valve in-line with the bolus pathway to ensure that a bolus procedure can only be performed when using a properly positioned special ...