Pump Chemotherapy for Colorectal Cancer

Recruiting at 45 trial locations

Overseen By Midhun Malla

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: Standard chemotherapy

Disqualifiers: Liver tumor burden >70%, Prior liver radiation, Prior HAI, Cirrhosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: Up to 5 years

408 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding hepatic arterial infusion (HAI) pump chemotherapy to standard chemotherapy can more effectively treat colorectal cancer that has spread to the liver and cannot be surgically removed. The HAI pump delivers a drug directly to the liver, targeting cancer cells more precisely. This study targets individuals with colorectal cancer that has spread only to the liver and who have already undergone a few months of standard chemotherapy. As a Phase 3 trial, this treatment represents the final step before FDA approval, providing access to potentially effective therapy before it becomes widely available.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does require that you have stable or responding disease on first-line chemotherapy, which suggests you may need to continue with your existing chemotherapy regimen.

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

Research shows that a hepatic arterial infusion (HAI) pump for chemotherapy is generally well-tolerated by patients. Studies have found that HAI treatment for colorectal cancer that has spread to the liver often leads to lasting positive results with few complications. Most people can undergo the treatment without major issues.

The chemotherapy drug used in the HAI pump is floxuridine. Research indicates that it is a potent drug with a higher risk of side effects. While effective, some side effects are expected, which is common with chemotherapy treatments.

The procedure to place the pump, which delivers chemotherapy directly to the liver, usually succeeds. This method aims to target the cancer more precisely, helping to control its spread in the liver.

In summary, despite some risks with floxuridine, the HAI pump method is generally well-tolerated and offers a focused approach to treating liver metastases in colorectal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal cancer?

Researchers are excited about the pump chemotherapy approach for colorectal cancer because it introduces a unique delivery method called hepatic arterial infusion (HAI). Unlike standard chemotherapy regimens such as FOLFOX and FOLFIRI that distribute drugs throughout the body, HAI delivers floxuridine directly to the liver, potentially increasing the drug's effectiveness against liver metastases while minimizing systemic side effects. This targeted delivery is particularly promising for patients with liver-dominant disease, offering a new hope for enhanced outcomes. Additionally, combining this method with standard chemotherapy regimens might improve overall treatment efficacy, providing a more comprehensive attack on the cancer.

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

Research shows that hepatic artery infusion (HAI) with floxuridine can be effective for patients with liver tumors from colorectal cancer. In this trial, participants in Arm A will receive HAI with floxuridine alongside standard chemotherapy. Studies have found that HAI can lead to better tumor shrinkage compared to regular chemotherapy. Specifically, HAI with floxuridine helps patients go longer without cancer recurrence. This method delivers chemotherapy directly to the liver, allowing for more precise targeting of tumors. Overall, evidence suggests that adding HAI to standard chemotherapy may help shrink or stabilize liver tumors in patients with colorectal cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Lidsky

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with colorectal cancer that has spread to the liver and can't be surgically removed may join. They should have stable or no extra liver disease, possibly small lung nodules, and must have had 3-6 months of initial chemotherapy with certain drugs. Those who've had new liver metastases within a year after adjuvant therapy for stage II-III colorectal cancer are also eligible.

Inclusion Criteria

My primary cancer tumor has not been removed.

My cancer cannot be removed with surgery.

Patient must meet specific laboratory criteria

Exclusion Criteria

Patient must not have certain medical conditions

All patients of childbearing potential must have a negative pregnancy test within 14 days prior to randomization

My liver metastases cannot be removed with a two-stage surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either hepatic arterial infusion (HAI) with floxuridine and standard chemotherapy or standard chemotherapy alone. Treatment includes surgery for HAI pump placement and regular CT scans.

Up to 5 years

Regular visits for chemotherapy administration and imaging

Follow-up

Participants are monitored for overall survival, progression-free survival, and response rate through regular imaging every 3 months.

Up to 5 years

Imaging every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Cetuximab
• Floxuridine
• Fluorouracil
• Intrahepatic Infusion Procedure
• Irinotecan
• Leucovorin
• Oxaliplatin
• Panitumumab

Trial Overview The PUMP trial is testing if adding pump chemotherapy (HAI) directly into the liver using floxuridine improves outcomes compared to standard chemotherapy alone in patients with unresectable colorectal liver metastases. The study will compare tumor shrinkage and stability between both treatments.

How Is the Trial Designed?

Group I: Arm A (HAI, floxuridine, standard chemotherapy) Experimental Treatment 11 Interventions

Patients undergo surgery to place the HAI pump, followed by SPECT/CT on study. Patients then receive floxuridine via the HAI pump on study. Patients also receive one of the following standard chemotherapy regimens per the treating physician: FOLFOX, FOLFIRI, or OX/IRI with or without cetuximab IV and/or panitumumab IV on study. Patients also undergo CT scans throughout the trial.

Group II: Arm B (standard chemotherapy) Active Control 8 Interventions

Patients receive one of the following standard chemotherapy regimens per the treating physician: FOLFOXIRI, FOLFOX, FOLFIRI, or OX/IRI with or without cetuximab IV, panitumumab IV, and/or bevacizumab IV on study. Patients also undergo CT scans throughout the trial.

Floxuridine is already approved in United States, European Union for the following indications:

Approved in United States as Floxuridine for:

• Metastatic colorectal cancer
• Gastrointestinal adenocarcinoma metastatic to the liver

Approved in European Union as Floxuridine for:

• Gastrointestinal adenocarcinoma metastatic to the liver

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 79 patients with advanced colorectal cancer, an alternating treatment schedule of 5-fluorouracil with leucovorin, oxaliplatin, and irinotecan achieved a 54% objective response rate, indicating significant efficacy in managing the disease.

The treatment was associated with manageable toxicity, with no grade 3/4 neurotoxicity and no toxic deaths reported, suggesting a safer profile compared to traditional sequential therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOX alternated with FOLFIRI as first-line chemotherapy for metastatic colorectal cancer. Aparicio, J., Fernandez-Martos, C., Vincent, JM., et al.[2022]

The evolution of chemotherapy for colorectal cancer has shifted from the single-agent use of 5-fluorouracil (5-FU) to more effective combination regimens that include irinotecan, oxaliplatin, and targeted agents like bevacizumab, significantly improving patient survival rates.

Combination therapies utilizing 5-FU as a base have been shown to enhance treatment outcomes, highlighting the importance of integrating newer drugs into established regimens for better management of colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current approaches to first-line treatment of advanced colorectal cancer. Goldberg, RM.[2019]

Five years after surgery and chemotherapy, about 10% more patients with Dukes C colon cancer are disease-free compared to those who did not receive treatment, highlighting the efficacy of adjuvant chemotherapy.

5-fluorouracil combined with folinic acid (5FU/FA) significantly improves survival rates for patients with disseminated colorectal cancer, doubling survival compared to best supportive care and enhancing quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Colorectal cancer: a controllable disease]. Bleiberg, H., Gerard, B.[2013]

Oral fluorinated pyrimidines, such as capecitabine and S-1, offer a more convenient and potentially less toxic alternative to traditional intravenous 5-fluorouracil (5-FU) chemotherapy, providing prolonged drug exposure at lower peak concentrations.

The review highlights that different oral fluoropyrimidines exhibit varying toxicity profiles compared to 5-FU, and ongoing phase III trials are essential to determine their effectiveness in treating colorectal cancer compared to standard 5-FU regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral fluoropyrimidines: a closer look at their toxicities. Macdonald, JS.[2019]

5-fluorouracil (5-FU) combined with leukovorin is commonly used for treating metastatic colorectal cancer, but it can cause severe gastrointestinal side effects, including stomatitis and diarrhea, which can be life-threatening in up to 30% of patients.

This case report highlights therapy-induced enteritis as a serious complication of 5-FU treatment, emphasizing the need for early recognition and intervention to prevent significant morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enteritis as a complication of adjuvant combination chemotherapy using 5-fluorouracil and leukovorin: clinical and helical computed tomographic features. Zamani, R., Heldmann, M.[2022]

Oxaliplatin, a new platinum analog, shows high effectiveness in treating metastatic colorectal cancer, particularly when used in combination with 5-FU and leucovorin, which has led to its approval in Europe for first- and second-line treatments.

This ongoing compassionate-use study aims to provide oxaliplatin to patients in the United States who have no adequate second- or third-line therapy options available, highlighting the urgent need for safety data and FDA approval for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin with 5-FU or as a single agent in advanced/metastatic colorectal cancer. Mitchell, EP.[2018]

Fluorouracil (5-FU) has been the standard treatment for advanced colorectal cancer for over 40 years, but only a small number of patients show a significant clinical response, highlighting the need for improved therapies.

New oral fluoropyrimidines and combination therapies with oxaliplatin or irinotecan have shown comparable efficacy to traditional 5-FU treatments while reducing side effects like febrile neutropenia and mucositis, suggesting a promising direction for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer: chemotherapy treatment overview. Royce, ME., Medgyesy, D., Zukowski, TH., et al.[2018]

5-Fluorouracil (5-FU) has been the standard treatment for colorectal cancer for 40 years, but its overall survival benefit remains limited to about 12 months, even with enhancements like leucovorin.

Capecitabine has been shown to be as effective as 5-FU and is now a first-line treatment, especially when combined with other agents like CPT-11 or oxaliplatin, which improve response rates and overall survival in patients with advanced colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of colorectal cancer metastasis: the role of chemotherapy. Xiong, HQ., Ajani, JA.[2019]

The FOLFOX regimen, which combines Leucovorin and fluorouracil with oxaliplatin, is a standard first-line treatment for metastatic colorectal cancer, but it has significant side effects including neutropenia and sensory neuropathy.

Immediate hypersensitivity reactions, such as anaphylaxis, can occur in up to 0.6% of patients receiving FOLFOX, highlighting the importance of monitoring for adverse effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[FOLFOX]. Mishima, H., Ikenaga, M., Tsujinaka, T., et al.[2013]

In a study of 89 patients with advanced colorectal cancer, the combination of infusional 5-fluorouracil (5-FU) and oxaliplatin showed the best overall survival, with a median survival time of 17 months, compared to 15 months for bolus 5-FU and 11 months for 5-FU with CPT-11.

The results suggest that infusional 5-FU can be effectively used as a foundation for sequential chemotherapy regimens, particularly when combined with oxaliplatin, while CPT-11 alone did not provide sufficient efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mayo regimen plus three different second-line chemotherapy regimens in sequential therapy in patients with advanced colorectal cancer (ACRC). Popov, IP., Jelic, SB., Matijasevic, MM., et al.[2018]

The combination of traditional chemotherapy agents like fluorouracil (5FU) with newer drugs such as irinotecan and oxaliplatin has significantly improved treatment effectiveness for colorectal cancer, leading to better patient outcomes.

Emerging targeted therapies are showing promise in reducing toxicity compared to traditional chemotherapy, and their integration into treatment protocols may extend survival rates for metastatic colorectal cancer patients from 2 to potentially 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The modern treatment of colorectal cancer. Present and future]. András, C., Farczádi, E., Szántó, J.[2018]

In a study involving 19 patients with metastatic colorectal cancer, the combination of irinotecan (CPT-11) and doxifluridine (5'-DFUR) showed manageable safety, with severe diarrhea occurring in only one patient, indicating a favorable safety profile for this regimen.

The recommended dosing for further studies was established at CPT-11 150 mg/m2 and 5'-DFUR 800 mg, based on the observed tolerability and efficacy in both murine models and human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential treatment with irinotecan and doxifluridine: optimal dosing schedule in murine models and in a phase I study for metastatic colorectal cancer. Mishima, H., Kato, T., Yanagisawa, M., et al.[2018]

A patient with metastatic rectal cancer experienced port thrombosis after receiving a mixed infusion of calcium folinate and 5-fluorouracil (5-FU) over 24 hours, highlighting potential complications of this treatment method.

Analysis of the catheter revealed calcium carbonate buildup, indicating that the combination of these two drugs may not be safe for routine clinical use without further validated clinical data on their compatibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Catheter occlusion by calcium carbonate during simultaneous infusion of 5-FU and calcium folinate. Bruch, HR., Esser, M.[2017]

In a phase II study involving 46 patients with advanced colorectal cancer resistant to previous treatments, the FOLFOX2 regimen (oxaliplatin, leucovorin, and 5-FU) achieved a high overall response rate of 46%, including one complete response and 20 partial responses.

The treatment was associated with manageable toxicities, primarily neutropenia (39%) and peripheral neuropathy (9%), indicating that while the regimen is effective, careful monitoring for these side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. de Gramont, A., Vignoud, J., Tournigand, C., et al.[2019]

Citations

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Reappraisal of hepatic arterial infusion in the treatment ... These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer.

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5-Fluorodeoxyuridine Experimental anticancer agent shown to have activity against a variety of malignant neoplasms, including mouse mammary tumors and colorectal carcinomas. Usage ...

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Floxuridine (Synonyms: 5-Fluorouracil 2'-deoxyriboside) Floxuridine (intraperitoneal injection; 0.5-1.25 mg/kg; once per day for 7 days or single dose) is sufficient to show statistically significant protection ...