IVLP with Oxaliplatin for Colorectal Cancer Spread to Lungs
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University Health Network, Toronto
Disqualifiers: Significant pulmonary disease, Pregnancy, others
No Placebo Group
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing a new method of delivering chemotherapy directly into the lungs during surgery to treat patients with colorectal cancer that has spread to the lungs. The goal is to kill cancer cells in the lung while minimizing side effects to other organs. The study will determine the safest dose of the chemotherapy drug oxaliplatin when delivered using this method.
Do I need to stop my current medications for this trial?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you are participating in another clinical trial, you cannot join this one.
What data supports the effectiveness of the drug oxaliplatin for colorectal cancer that has spread to the lungs?
Oxaliplatin has shown promising results in treating advanced colorectal cancer, with response rates of up to 60% when combined with other drugs like fluorouracil (5-FU). It has been effective in increasing the time before the cancer progresses, although it does not significantly improve overall survival.
12345Is oxaliplatin safe for use in humans?
Oxaliplatin is generally safe for use in humans, but it can cause side effects like nerve damage (neuropathy), low white blood cell counts (neutropenia), and allergic reactions. These side effects are usually manageable, but some patients may need to stop treatment if they experience severe reactions.
23567How does the drug oxaliplatin differ from other treatments for colorectal cancer that has spread to the lungs?
The treatment involves using oxaliplatin, a platinum-based drug, which is unique because it is often more effective than other platinum drugs like cisplatin, especially in cases where the cancer has become resistant to other treatments. This trial specifically explores its use for colorectal cancer that has spread to the lungs, a condition for which there are no standard treatments, making this approach novel.
12358Eligibility Criteria
This trial is for people under 71 with colorectal cancer that has spread to both lungs but not beyond, except possibly the liver. They should be relatively fit (ECOG 0-2) and have at least three lung lesions. It's not for those with a history of severe lung disease, heart issues, or who've had high doses of oxaliplatin before.Inclusion Criteria
3 or more lung lesions in total
I have been diagnosed with colorectal cancer.
I am able to care for myself and move around.
+3 more
Exclusion Criteria
Hypersensitivity to oxaliplatin
I am allergic or cannot take cefazolin or methylprednisolone but can join without taking them.
I am either 71 years old or older, or younger than 18.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive oxaliplatin via In Vivo Lung Perfusion (IVLP) in one lung during surgery to test safety and determine the appropriate dose
1 day
1 visit (in-person, during surgery)
Immediate Post-Treatment Monitoring
Participants are monitored for acute lung injury and side effects in the first 72 hours post-treatment
72 hours
Continuous monitoring (in-patient)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests a new method called IVLP where chemotherapy (oxaliplatin) is delivered directly into one lung during surgery to target cancer cells while minimizing harm to other organs. The dose starts low and increases until it causes serious but temporary side effects.
1Treatment groups
Experimental Treatment
Group I: IVLP in single lungExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Health Network, Toronto General HospitalToronto, Canada
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Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
References
Novel combinations with oxaliplatin. [2022]Oxaliplatin (Eloxatin) is a novel antineoplastic platinum derivative that may exert its cytotoxic effects by blocking DNA replication/transcription, thus resulting in cell death in proliferating cells, as well as apoptosis. Oxaliplatin is often more potent than other platinums such as cisplatin (Platinol) in vitro, and shows greater efficacy in preclinical studies against many tumor cell lines, including some that are resistant to cisplatin and carboplatin (Paraplatin). Oxaliplatin is approved for use with the fluoropyrimidines in the treatment of metastatic colorectal cancer in Asia, Latin America, and Europe. In light of the broad efficacy of oxaliplatin in several solid tumors and the encouraging preclinical data on combination therapy with novel agents (e.g., thymidylate synthase inhibitors, epidermal growth factor-receptor antagonists, microtubule interactive agents), this article will review the published literature on novel combinations that have been tested in the laboratory and/or the clinic.
Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European compassionate-use program. [2020]To provide evidence for the therapeutic efficacy of oxaliplatin (Eloxatin) when given as a 2-6-hour i.v. infusion, alone or in combination with 5-fluorouracil/folinic acid (5-FU +/- FA) in patients with advanced colorectal carcinoma (ACRC) who have failed 5-FU-based therapy. To confirm the safety of the drug and its combination in an extended-access context.
Oxaliplatin: a review of its use in combination therapy for advanced metastatic colorectal cancer. [2022]Oxaliplatin (Eloxatin) is the only platinum compound to show clinical activity in colorectal cancer. The efficacy of a combination of oxaliplatin with various schedules of fluorouracil (5-FU)/folinic acid (FA) as first- or second-line treatment for advanced metastatic colorectal cancer has been investigated in large phase III trials. FOLFOX4 (an oxaliplatin/5-FU/FA regimen) as first-line therapy (n = 795) was superior to irinotecan/5-FU/FA (IFL). Response rates were 45% vs 31%, and median progression-free survival duration was 8.7 vs 6.9 months. The survival advantage shown by FOLFOX4 over the irinotecan combination (median survival duration 19.5 vs 14.8 months) may be confounded by differences in post-study treatment but equivalent efficacy is supported by another phase III trial of oxaliplatin and irinotecan combinations. As first-line therapy, oxaliplatin added to various 5-FU/FA regimens more than doubled the response rates from 16-22.6% to 48.3-53% and the median duration of progression-free survival was significantly longer with oxaliplatin/5-FU/FA than 5-FU/FA alone (7.9-9 versus 5.3-6.2 months, respectively). In disease resistant to irinotecan-based therapies, the oxaliplatin (FOLFOX4) regimen had superior efficacy to 5-FU/FA alone in a pivotal phase III trial (n = 816). Response rates and median durations of progression-free survival were 9.6% vs 0.7% and 5.6 vs 2.6 months, respectively. An oxaliplatin-induced cumulative peripheral sensory neuropathy (evident when total dose reaches approximate, equals 800 mg/m(2)) is dose limiting. The most frequently occurring grade 3 or 4 toxicities in oxaliplatin/5-FU/FA-recipients were neutropenia (up to 48%) and neurological toxicities (up to 18%). Gastrointestinal effects (diarrhoea [ approximate, equals 12%], nausea, vomiting, or mucositis/stomatitis [up to 6%]) are manageable. Withdrawals from oxaliplatin treatment were due to neuropathy (up to 10%), diarrhoea and/or vomiting (1%) or cutaneous toxicity (1%).
The efficacy and toxicity of FOLFOX regimen (a combination of leucovorin and fluorouracil with oxaliplatin) as first-line treatment of metastatic colorectal cancer. [2013]Oxaliplatin is the third-generation platinum complex to be active in advanced colorectal cancer. In Japan, it was approved in April 2005. FOLFOX regimen(a combination of leucovorin and fluorouracil with oxaliplatin) has been one of the standard chemotherapy regimens for metastatic colorectal cancer.
Efficacy of oxaliplatin in the treatment of colorectal cancer. [2022]Colorectal cancer is one of the leading causes of cancer death. The mainstay of chemotherapy in colorectal cancer patients for the past 40 years has been fluorouracil (5-FU). Oxaliplatin (Eloxatin) is a novel platinum compound with promising activity in colorectal cancer. As a single agent, oxaliplatin has produced response rates of 12% to 24% in patients with previously untreated advanced colorectal cancer, and 10% to 11% in patients with relapsed or refractory advanced colorectal cancer. In phase II trials, oxaliplatin combined with 5-FU, with or without leucovorin, was associated with response rates of 60% and higher when used as front-line therapy, and when used in patients with relapsed or refractory advanced colorectal cancer, response rates ranged from 25% to 50%. In the front-line setting, two randomized trials of 5-FU and leucovorin, with or without oxaliplatin, demonstrated that the addition of oxaliplatin significantly increases response rate and time to tumor progression, but not survival, over 5-FU plus leucovorin alone. The reasons for this discrepancy are unclear, and several possibilities are being considered. Additional phase III trials are underway to clarify the contribution of oxaliplatin in the treatment of patients with locally advanced and metastatic colorectal cancer.
Management of allergic reactions to oxaliplatin in colorectal cancer patients. [2018]Allergic reactions to oxaliplatin (Eloxatin) may be sufficiently severe to prevent patients from continuing treatment. Oxaliplatin is a key drug that improves the survival of colorectal cancer patients; however,a uniform approach to prevent allergic reactions in patients using this drug has not been established. We investigated the safety and efficacy of our own preventive strategy in colorectal cancer patients receiving the 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX4) regimen. Each patient received the primary prevention regimen before oxaliplatin infusion during the first cycle and diphenhydramine after cycle 4. Patients who experienced grade 1 or 2 allergic reactions subsequently received the secondary prevention regimen with a higher dose of dexamethasone and prolonged oxaliplatin infusion to allow continued treatment. Oxaliplatin was discontinued in patients with grade 3 or 4 allergic reactions. Forty-eight patients (17.6%) developed allergic-reactions,and 30 patients underwent retreatment with the secondary prevention regimen. Nineteen patients (63.3%) showed no reactions during at least 2 cycles; most could be treated for 4 months longer than could patients who did not respond to secondary prevention. This preventive strategy was both safe and effective, allowing patients to continue treatment without detriment to their quality of life.
[Relative dose intensity of FOLFOX4 regimen]. [2018]Oxaliplatin (L-OHP) is one of the key drugs against advanced, recurrent colorectal cancer, and FOLFOX4 regimen combination of l-leucovorin (l-LV)and 5-fluorouracil (5-FU)with oxaliplatin is a standard therapy in colorectal cancer. We performed a retrospective study that researched adverse events and relative dose intensity(RDI)to evaluate safety and feasibility of FOLFOX4 regimen.
[Oxaliplatin -- A 10-Year Trajectory]. [2018]Oxaliplatin(Elplat(®)iv infusion solution)is a third-generation 1,2-DACH-platinum derivative. A number of international clinical trials have investigated the effects of this drug for each of its four indications. Building on the results of these earlier studies, much research has also been carried out in Japan in terms of developing and accumulating evidence on oxaliplatin. This report reviews the trajectory of its use over the last 10-years and considers its future potential.