M9241 + HAIP Chemotherapy for Liver Cancers

Recruiting in Palo Alto (17 mi)

Overseen by Jonathan M Hernandez, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents, rIL-12

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Background: One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug PDS01ADC can improve the treatment. The drug triggers the immune system to fight cancer.\<TAB\> Objective: To see if treatment with HAIPs to deliver liver-directed chemotherapy in combination with PDS01ADC is effective for certain cancers. Eligibility: People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver. Design: Participants will be screened with: Medical history Physical exam Blood tests Pregnancy test (if needed) Tumor biopsy (if needed) Electrocardiogram Computed tomography (CT) scans Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen. Participants will have chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. PDS01ADC will be injected under the skin every 4 weeks. They will get systemic chemotherapy through an IV or mediport every 2 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects. Participants will have 2 study visits each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests. Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

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.

What data supports the effectiveness of the treatment M9241 + HAIP Chemotherapy for Liver Cancers?

The Hepatic Artery Infusion Pump (HAIP) has shown improved outcomes in treating colorectal liver metastases, suggesting potential benefits for liver cancers. Although specific data for M9241 in this combination is not provided, HAIP's effectiveness in similar conditions supports its use. ^{1 2 3 4 5}

Is the hepatic artery infusion pump (HAIP) chemotherapy generally safe for humans?

The safety of the hepatic artery infusion pump (HAIP) chemotherapy has been assessed in various studies, showing it is a specialized therapy for liver metastases with some uncertainty about its safety and feasibility at different centers. While it has been associated with improved outcomes, there are concerns about complications and limited survival benefits, which led to its decreased use in the past. ^{1 2 3 4 5}

What makes the M9241 + HAIP treatment unique for liver cancers?

The M9241 + HAIP treatment is unique because it uses a hepatic artery infusion pump (HAIP) to deliver chemotherapy directly to the liver, which can be more effective for liver cancers that are not suitable for surgery. This method allows for higher concentrations of the drug to reach the liver with potentially fewer side effects compared to traditional systemic chemotherapy. ^{1 2 3 4 5}

Research Team

Jonathan M Hernandez, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14080

Patients Recruited

41,180,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

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]

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]

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]

References

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

Hepatic artery infusion pump in the treatment of liver metastases. [2018]

2. United States 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. [2022]

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

Short-Term Risk of Performing Concurrent Procedures with Hepatic Artery Infusion Pump Placement. [2021]

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

Robotic hepatic arterial infusion pump placement. [2018]

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

Salvage regional therapy using hepatic artery infusion pump in unresectable chemotherapy resistant colorectal liver metastases. [2022]