RECRUITING

Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial

Conditions

Metastatic Colorectal Carcinoma Metastatic Malignant Neoplasm in the Liver Stage IV Colorectal Cancer AJCC v8 Unresectable Colorectal Carcinoma

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs 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. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.

Official Title

A Randomized Phase III Study of Systemic Therapy With or Without Hepatic Arterial Infusion for Unresectable Colorectal Liver Metastases: The PUMP Trial

Quick Facts

Study Start:2023-10-19

Study Completion:2034-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05863195

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patient must be \>= 18 years of age * Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC). * Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes). * NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study. * Patient may have calcified pulmonary nodules, and/or =\< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =\< 6 mm in maximal axial dimension. * Patient's primary tumor may be in place. * Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer. * NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab. * Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria * Patient must meet the following criteria for technical unresectability: * A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments. * NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease. * Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization. * Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation. * Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to protocol randomization) * Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 14 days prior to protocol randomization) * Platelets \>= 100,000/mcL (obtained =\< 14 days prior to protocol randomization) * Total Bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to protocol randomization) * Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to protocol randomization) * Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 14 days prior to protocol randomization) * Calcium \>= institutional lower limit of normal (LLN) * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study	* Patient must not have a liver tumor burden exceeding 70% of total liver volume. * Patient must not have had prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 2 weeks prior to randomization). * Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE). * Patient must not have had prior treatment with HAI/floxuridine (FUDR) * Patient must not have microsatellite instability-high (MSI-H) colorectal cancer. * Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS). * Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture. * Patient must not have any serious medical problems which would preclude receiving the protocol treatment or would interfere with the cooperation with the requirements of this trial. * Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. * All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy. * A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). * Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study.

Inclusion Criteria

Exclusion Criteria

* Patient must be \>= 18 years of age
* Patient must have confirmed unresectable liver confined metastatic colorectal cancer (CRC).
* Patient must not have radiographically or clinically evident extrahepatic disease (including but not limited to radiographically positive periportal lymph nodes).
* NOTE: Patients found to have positive periportal nodes at the time of HAI placement can remain on study.
* Patient may have calcified pulmonary nodules, and/or =\< 5 indeterminate and stable (for a minimum of 3 months on chemotherapy) pulmonary nodules each measuring =\< 6 mm in maximal axial dimension.
* Patient's primary tumor may be in place.
* Patient must have received 3-6 months of previous first-line chemotherapy that meet one of the following three criteria: a) have received at least 6 but no more than 12 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 14 days) OR b) have received at least 4 but no more than 8 cycles of first-line cytotoxic chemotherapy (where 1 cycle = 21 days) OR c) have developed new colorectal liver metastases (CRLM) within 12 months of completing adjuvant systemic therapy for stage II-III colorectal cancer.
* NOTE: First-line chemotherapy may have included any of the following regimens as listed in the National Comprehensive Cancer Network (NCCN) Guidelines: leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin (FOLFOX) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, and irinotecan (FOLFIRI) (or equivalent), leucovorin calcium (calcium folinate), 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI), each with or without any of the following: bevacizumab, cetuximab, or panitumumab.
* Patient must have stable or responding disease on first-line chemotherapy by RECIST 1.1 criteria
* Patient must meet the following criteria for technical unresectability:
* A margin-negative resection requires resection of three hepatic veins, both portal veins, or the retrohepatic vena cava OR a resection that leaves less than two adequately perfused and drained segments.
* NOTE: Institutional multidisciplinary review is required to confirm unresectability and rule out radiographically positive extrahepatic disease.
* Patient must undergo CT angiography (chest/abdomen/pelvis) to confirm acceptable hepatic arterial anatomy for HAI and to rule out extrahepatic disease within 4 weeks prior to randomization.
* Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 and be clinically fit to undergo surgery as determined by the pre-operative evaluation.
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (obtained =\< 14 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to protocol randomization)
* Total Bilirubin =\< 1.5 mg/dL (obtained =\< 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal (ULN) (obtained =\< 14 days prior to protocol randomization)
* Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \>= 50 mL/min calculated by the Cockcroft-Gault method (obtained =\< 14 days prior to protocol randomization)
* Calcium \>= institutional lower limit of normal (LLN)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial. Testing for HIV is not required for entry onto the study

* Patient must not have a liver tumor burden exceeding 70% of total liver volume.
* Patient must not have had prior radiation to the liver (prior radiation therapy to the pelvis is acceptable if completed at least 2 weeks prior to randomization).
* Patient must not have had prior trans-arterial bland embolization, chemoembolization (TACE) or radioembolization (TARE).
* Patient must not have had prior treatment with HAI/floxuridine (FUDR)
* Patient must not have microsatellite instability-high (MSI-H) colorectal cancer.
* Patient must not have CRLM that could be resected with 2-stage hepatectomy, including associating liver partition and portal vein ligation (ALPPS).
* Patient must not have an active infection, serious or non-healing active wound, ulcer, or bone fracture.
* Patient must not have any serious medical problems which would preclude receiving the protocol treatment or would interfere with the cooperation with the requirements of this trial.
* Patient must not have cirrhosis and/or clinical or radiographic evidence of portal hypertension
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
* All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
* Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study.

Contacts and Locations

Principal Investigator

Michael Lidsky

PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Study Locations (Sites)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233

United States

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045

United States

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180

United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146

United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442

United States

UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, 33021

United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136

United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176

United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

Memorial Hospital East

Shiloh, Illinois, 62269

United States

IU Health North Hospital

Carmel, Indiana, 46032

United States

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202

United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536

United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109

United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503

United States

Mayo Clinic in Rochester

Rochester, Minnesota, 55905

United States

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

Siteman Cancer Center-South County

Saint Louis, Missouri, 63129

United States

Siteman Cancer Center at Christian Hospital

Saint Louis, Missouri, 63136

United States

Siteman Cancer Center at Saint Peters Hospital

Saint Peters, Missouri, 63376

United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Commack

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester

Harrison, New York, 10604

United States

Mount Sinai Hospital

New York, New York, 10029

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553

United States

Duke University Medical Center

Durham, North Carolina, 27710

United States

Case Western Reserve University

Cleveland, Ohio, 44106

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212

United States

West Penn Hospital

Pittsburgh, Pennsylvania, 15224

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232

United States

Parkland Memorial Hospital

Dallas, Texas, 75235

United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390

United States

Collaborators and Investigators

Sponsor: ECOG-ACRIN Cancer Research Group

Michael Lidsky, PRINCIPAL_INVESTIGATOR, ECOG-ACRIN Cancer Research Group

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-19

Study Completion Date2034-06-30

Study Record Updates

Study Start Date2023-10-19

Study Completion Date2034-06-30

Terms related to this study

Additional Relevant MeSH Terms

Metastatic Colorectal Carcinoma
Metastatic Malignant Neoplasm in the Liver
Stage IV Colorectal Cancer AJCC v8
Unresectable Colorectal Carcinoma