Pump Chemotherapy for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
+39 other locations
Overseen byMichael Lidsky
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the drug combination used in pump chemotherapy for colorectal cancer?
Research shows that combining oxaliplatin with 5-FU and leucovorin improves response rates and time to progression in colorectal cancer patients compared to using 5-FU and leucovorin alone. Additionally, targeted agents like bevacizumab enhance the outcomes of 5-FU-based regimens, further supporting the effectiveness of this drug combination.
12345What safety data exists for pump chemotherapy treatments for colorectal cancer?
Pump chemotherapy treatments, like those involving oxaliplatin, leucovorin, and 5-fluorouracil (5-FU), can cause side effects such as neutropenia (low white blood cell count), peripheral neuropathy (nerve damage), nausea, diarrhea, and mucositis (inflammation of the digestive tract). Irinotecan and 5-FU can also cause diarrhea, which may be severe. It's important to monitor for these side effects during treatment.
678910What makes the pump chemotherapy treatment for colorectal cancer unique?
Pump chemotherapy for colorectal cancer is unique because it combines multiple drugs like Floxuridine, Fluorouracil, Irinotecan, Leucovorin, and Oxaliplatin, which are administered through a pump, allowing for continuous infusion. This method can enhance the effectiveness of the treatment by maintaining a steady drug level in the body, potentially improving outcomes compared to traditional bolus (single large dose) administration.
311121314Eligibility Criteria
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
+10 more
Exclusion Criteria
My liver metastases cannot be removed with a two-stage surgery.
Patient must not have certain medical conditions
All patients of childbearing potential must have a negative pregnancy test within 14 days prior to randomization
+8 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (HAI, floxuridine, standard chemotherapy)Experimental Treatment11 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 Control8 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Siteman Cancer Center at Christian HospitalSaint Louis, MO
Siteman Cancer Center at West County HospitalCreve Coeur, MO
Fox Chase Cancer CenterPhiladelphia, PA
Parkland Memorial HospitalDallas, TX
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
ECOG-ACRIN Cancer Research GroupLead Sponsor
National Cancer Institute (NCI)Collaborator
References
FOLFOX alternated with FOLFIRI as first-line chemotherapy for metastatic colorectal cancer. [2022]5-fluorouracil (5-FU), irinotecan, and oxaliplatin are the most active drugs in advanced colorectal cancer (CRC), and survival is improved with patient exposure to all of them. The efficacy and safety of an alternating schedule of continuous-infusion 5-FU with leucovorin (LV) plus oxaliplatin (ie, FOLFOX regimen) or irinotecan (ie, FOLFIRI regimen) was assessed in the first-line setting.
Current approaches to first-line treatment of advanced colorectal cancer. [2019]The multiplicity of chemotherapy regimens currently available to treat colorectal cancer in the first-line setting precludes the identification of a single standard regimen for front-line therapy. The previous standard, 5-fluorouracil (5-FU), formerly the only agent with any significant activity against colorectal cancer, is now the base for newer combination regimens that are improving survival in this disease. When irinotecan and oxaliplatin were proven to be active in colorectal cancer, the pursuit of combination regimens began. Targeted agents such as bevacizumab also show activity and improve the outcome of 5-FU-based regimens. The history and development of 5-FU-based treatment regimens that include the newer drugs irinotecan, oxaliplatin, and bevacizumab are discussed in light of the impact these advances have made in the treatment of colorectal cancer
[The modern treatment of colorectal cancer. Present and future]. [2018]The modern treatment of colorectal cancer. Present and future. Fluorouracyl has been the mainstay of treatment for colorectal cancer for decades. The addition of folinic acid to 5FU, the use of infusional, rather than bolus 5FU, and the combination of new active agents such as irinotecan and oxaliplatin with 5FU/LV have each led to increase in effectivity. Oral formulations of fluoropyrimidines can replace the infusional 5FU therapy with better convenience. The authors review the current progress with the use of novel molecular targeted therapies that are tumor specific with better toxicity profile than chemotherapy. The integration of the new biological response modifier therapeutic possibilities in the chemotherapy protocols may result prolongation in survival, in metastatic patients the presently 2 years survival will approach 3 years. Combining these drugs with chemotherapeutics in the adjuvant setting we hope to raise further the presently achieved 78% of 3 years disease free survival by oxaliplatin plus 5FU therapy. As the variation of agents has been increased, choosing the most effective treatment strategy has become increasingly complex.
Oxaliplatin with 5-FU or as a single agent in advanced/metastatic colorectal cancer. [2018]No adequate second- or third-line therapy is available in the United States for patients with metastatic colorectal cancer and disease progression following treatment with fluorouracil (5-FU)-based therapy and an irinotecan (CPT-11, Camptosar)-containing regimen, or a combination of the two. Oxaliplatin (Eloxatin), a new platinum analog, has demonstrated high activity in the treatment of colorectal cancer, especially when combined with 5-FU and leucovorin. The combination of oxaliplatin and 5-FU/leucovorin has been approved in Europe for the first- and second-line treatment of colorectal cancer. This compassionate-use study was initiated because of the unavailability of the agent in the United States and inadequate US safety data. The following review summarizes data from this ongoing study, the primary focus of which is to provide oxaliplatin for compassionate use until it receives US Food and Drug Administration approval and becomes available commercially.
Colorectal cancer: chemotherapy treatment overview. [2018]Fluorouracil (5-FU) has remained the standard therapy for the treatment of advanced colorectal cancer for over 40 years. Unfortunately, only a minority of patients experience objective clinical response. Discussed herein are attempts to improve on the activity of 5-FU by biochemically modulating its action. In addition, novel agents for the treatment of advanced colorectal cancer (oral fluoropyrimidines, oxaliplatin, and irinotecan) are discussed. Oral fluoropyrimidines (UFT plus leucovorin, capecitabine, eniluracil plus oral 5-FU) provide the convenience of oral delivery with a marked reduction in febrile neutropenia and mucositis. Recent randomized trials with these agents have demonstrated therapeutic activity that is comparable with intravenous schedules of 5-FU plus leucovorin. Compared to 5-FU, both oxaliplatin and irinotecan have uniquely different mechanisms of action and have demonstrated clinical activity in patients whose disease has progressed with 5-FU treatment. Combinations of either irinotecan or oxaliplatin plus 5-FU/leucovorin have demonstrated that the addition of these agents to 5-FU/leucovorin improves response rates and time to progression compared to 5-FU/leucovorin alone. Combination chemotherapy regimens with these novel agents are rapidly being introduced into the adjuvant setting.
Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. [2019]Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.
Sequential treatment with irinotecan and doxifluridine: optimal dosing schedule in murine models and in a phase I study for metastatic colorectal cancer. [2018]Irinotecan (CPT-11) and doxifluridine (5'-DFUR) are active agents against colorectal cancer. Each drug, however, has the possibility of causing diarrhea.
Oral fluoropyrimidines: a closer look at their toxicities. [2019]Patient preferences, quality of life issues, and economic considerations are driving the development of orally administered chemotherapy. Oral fluorinated pyrimidines, which have been used in Japan, are attracting increasing interest as a means to provide convenient, less toxic treatment without compromising efficacy. The oral fluoropyrimidines provide prolonged 5-fluorouracil (5-FU) exposure at lower peak concentrations than those observed with bolus intravenous administration. Moreover, depending on the dose schedule, the pharmacokinetics of the oral fluoropyrimidines may mimic the pharmacokinetics of continuous-infusion 5-FU. This review focuses on the toxicity profiles of five emerging oral fluoropyrimidine antineoplastic drugs: combined uracil and tegafur (UFT), capecitabine, eniluracil, S-1, and emitefur (BOF-A2). Different patterns of toxicities emerge from an analysis of the clinical trials of these agents relative to 5-FU administered as an intermittent intravenous bolus or as continuous infusion. The results of ongoing phase III trials comparing the oral fluoropyrimidines with conventional regimens of 5-FU plus leucovorin and 5-FU by continuous intravenous infusion are necessary before their therapeutic role in the management of colorectal carcinoma can be defined.
Enteritis as a complication of adjuvant combination chemotherapy using 5-fluorouracil and leukovorin: clinical and helical computed tomographic features. [2022]The combination of 5-flourouracil (5-FU) and leukovorin is widely used as adjuvant chemotherapy for metastatic colorectal carcinoma. The most common clinical side effects of 5-FU are related to its gastrointestinal toxicity, chiefly stomatitis and diarrhea. The latter may be severe in up to 30% and occasionally is life-threatening. We describe a case of therapy-induced enteritis presenting as acute abdominal pain and present the computed tomographic (CT) findings. In light of the prevalence of this regimen, the potential morbidity of this complication, and a paucity of CT examples in the radiologic literature, this case illustrates an important adverse effect of this medication. Early recognition and treatment should avoid significant morbidity and mortality.
[FOLFOX]. [2013]In metastatic colorectal cancer, a combination of Leucovorin (LV) and fluorouraci (l FU) with oxaliplatin (FOLFOX) is a standard first-line regimen. The two limiting toxicities of FOLFOX are neutropenia and the specific reversible sensory neuropathy of oxaliplatin. The cumulative neurotoxicity often requires therapy to be stopped. Immediate hypersensitive reactions (anaphylaxis) have been noted as often as to 0.6 percent. We should pay sufficient attention to side effects of FOLFOX.
[Colorectal cancer: a controllable disease]. [2013]Colorectal cancer is one of the most frequent cancers in western countries. Five years after curative surgery and adjuvant chemotherapy, about 10% more patients with Dukes C colon cancer are free of disease compared to the control group. Several regimens using 5-fluorouracil with folinic acid (5FU/FA) or levamisole are available. For patients with disseminated disease. 5FU/FA based treatments allows a doubling in survival as compared to best supportive care. Moreover, quality of life is significantly improved. New agents are upcoming. Tomudex seems to be equivalent to 5FU/FA but easier to administer. CPT-11 or oxaliplatin have been investigated in second line after failure of 5FU/FA. The available data suggest that median survival is prolonged by ten months, in addition to what was already obtained in first line with 5FU/FA. Colorectal cancer must be revisited. An active approach of our patients should allow to reduce the incidence of the disease, to increase the number of disease free patients 5 years after surgery, to prolong survival and improve the quality of life of those who will develop metastatic disease.
Mayo regimen plus three different second-line chemotherapy regimens in sequential therapy in patients with advanced colorectal cancer (ACRC). [2018]As the number of active drugs for colorectal cancer increases, we continually revisit the question of how best to integrate them. We investigated whether sequential chemotherapy consisting of only bolus plus infusional 5-fluorouracil/folinic acid could be comparable, concerning overall survival, to sequential chemotherapy consisting of bolus 5-fluorouracil/folinic acid plus "new-generation" drugs like CPT-11 or oxaliplatin. Patients with histologically verified locally advanced disease and/or metastatic colorectal adenocarcinoma, without possibility for surgical resection, were eligible for the study. The treatments were: Cohort A--Mayo Clinic Regimen (MCR) in first line, "de Gramont" regimen in second line; Cohort B--MCR in first line, CPT-11 (350mg/m2) in second line; Cohort C--MCR in first line, oxaliplatin (85mg/m2) plus "de Gramont" regimen in second line. A total of 89 patients received first plus second line chemotherapy and all of them were analyzed for survival. Number of patients/cohort: A-32 B-27; C-30. The median survival time of the patients was 15, 11, and 17 months for the patients in cohorts A, B, and C, respectively. Survival of the patients in cohort C was significantly better than survival of the patients in cohort B (log-rank test, p=0.04). There was not a significant difference in overall survival between the cohorts A vs. C (log-rank test, p=0.52) and B vs. C (log-rank test, p=0.27). It is conceivable that infusional HD 5-FU could serve as a basis for first and second-line protocols in which other drugs are added to this regimen. Infusional 5-FU plus oxaliplatin in sequential pattern of application after bolus 5-FU has the best overall survival in comparison to other cohorts. CPT-11 applied as a single drug, was not effective enough in comparison to other treatment options.
Treatment of colorectal cancer metastasis: the role of chemotherapy. [2019]5-Fluorouracil (5-FU) has been the main chemotherapeutic agent for the treatment of colorectal cancer for four decades with modest efficacy. Modulation of 5-FU by leucovorin or continuous infusion improves the response rate, but overall survival duration remains approximately 12 months. Many oral fluoropyrimidines have been studied, including capecitabine, UFT, S-1, and Eniluracil. Capecitabine has demonstrated equivalent efficacy with 5-FU and has been approved as first line treatment. The combinations of capecitabine with CPT-11 or oxaliplatin are being developed. CPT-11 demonstrated non-crossover resistance with 5-FU and was proven to be effective treatment for patients who received prior 5-FU. CPT-11 in combination with 5-FU has demonstrated improved response rate and overall survival duration over 5-FU or CPT-11. Oxaliplatin plus 5-FU has offered another effective treatment option for colorectal cancer. Both 5-FU plus leucovorin in combination with CPT-11 or oxaliplatin are widely used first-line chemotherapies for advanced colorectal cancer. Optimal combinations and sequences of treatment are being studied, since several effective regimens have become available.
Catheter occlusion by calcium carbonate during simultaneous infusion of 5-FU and calcium folinate. [2017]The treatment of colorectal cancer with administration of a 2-h infusion of calcium folinate followed by a 24-h infusion of 5-fluorouracil (5-FU) is a standard therapy. Based on newly published data we have applied an infusion of both compounds, 5-FU and calcium folinate, mixed together in an ambulatory pump.