IVLP with Oxaliplatin for Colorectal Cancer Spread to Lungs

Overseen By Jennifer K Lister

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Disqualifiers: Significant pulmonary disease, Pregnancy, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to deliver chemotherapy directly to the lungs during surgery for colorectal cancer that has spread there. The goal is to determine if this method, called In Vivo Lung Perfusion (IVLP), can safely target lung cancer cells without affecting other organs. The trial administers a chemotherapy drug called oxaliplatin (also known as Eloxatin) to one lung while monitoring for side effects. It is suitable for individuals with colorectal cancer who have at least three lung lesions and no other cancer spread, except possibly to the liver. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

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 prior data suggests that this IVLP technique is safe for delivering chemotherapy to the lungs?

Research has shown that using the IVLP technique to deliver oxaliplatin directly into the lungs is promising. A previous study with patients who had sarcoma demonstrated that high doses of oxaliplatin could be sent to the lungs without causing side effects in other parts of the body.

Studies have found that this technique targets cancer cells in the lungs, potentially leading to fewer side effects compared to traditional chemotherapy that affects the whole body. Participants in these studies were closely monitored to ensure side effects were not severe.

Overall, these findings suggest that the treatment is well-tolerated when administered directly to the lungs. However, since this is an early-stage study, participants are carefully monitored to determine the safest dose. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using oxaliplatin for colorectal cancer that has spread to the lungs because it employs a unique delivery method called isolated lung perfusion (IVLP). Unlike standard chemotherapy, which circulates throughout the entire body, IVLP delivers oxaliplatin directly to a single lung. This targeted approach aims to maximize the drug's impact on cancer cells in the lung while minimizing side effects on the rest of the body. This could potentially lead to more effective treatment outcomes with fewer systemic effects compared to traditional chemotherapy methods.

What evidence suggests that the IVLP technique is effective for colorectal cancer spread to the lungs?

Research has shown that delivering the drug oxaliplatin directly into the lungs using In Vivo Lung Perfusion (IVLP) could effectively target cancer cells in patients with colorectal cancer. This trial will study the use of IVLP in a single lung to attack cancer cells while minimizing side effects to other parts of the body. Previous studies found that oxaliplatin, when combined with other drugs, can extend patients' lives by several months. However, when administered through IVLP, some patients experienced mild to significant lung injury, necessitating careful dose monitoring. Early results suggest this targeted method could be promising, but more research is needed to confirm its efficacy and safety. ^{1 5 6 7 8}

Who Is on the Research Team?

Marcelo Cypel, MD MSc

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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.

Exclusion Criteria

Hypersensitivity to oxaliplatin

I am allergic or cannot take cefazolin or methylprednisolone but can join without taking them.

Left Ventricular Ejection Fraction <50%

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Oxaliplatin

Trial Overview 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.

How Is the Trial Designed?

Group I: IVLP in single lung Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study involving 206 patients with advanced colorectal carcinoma who had previously failed 5-FU-based therapy, the addition of oxaliplatin to 5-FU +/- folinic acid resulted in a 25.5% objective response rate, demonstrating its efficacy as a salvage therapy.

The median overall survival for patients receiving oxaliplatin combined with 5-FU +/- FA was 9.6 months, indicating that this treatment can provide significant benefits for patients resistant to prior fluoropyrimidine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Brienza, S., Bensmaïne, MA., Soulié, P., et al.[2020]

A preventive strategy involving dexamethasone and diphenhydramine was implemented for colorectal cancer patients receiving oxaliplatin, resulting in 63.3% of patients with prior allergic reactions being able to continue treatment without further issues.

Out of 48 patients who experienced allergic reactions, those who responded to the secondary prevention regimen were able to extend their treatment duration by an average of 4 months, demonstrating the strategy's safety and efficacy in maintaining quality of life during cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of allergic reactions to oxaliplatin in colorectal cancer patients. Suenaga, M., Mizunuma, N., Shinozaki, E., et al.[2018]

Oxaliplatin combined with 5-FU/FA significantly improves response rates and progression-free survival in patients with advanced metastatic colorectal cancer, showing a response rate of 45% compared to 31% for irinotecan/5-FU/FA in a study of 795 patients.

While oxaliplatin can cause dose-limiting neurotoxicity, its overall tolerability is manageable, making it a valuable first- or second-line treatment option for colorectal cancer, especially in patients who have failed irinotecan-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxaliplatin: a review of its use in combination therapy for advanced metastatic colorectal cancer. Simpson, D., Dunn, C., Curran, M., et al.[2022]

Oxaliplatin, when combined with fluorouracil (5-FU), has shown significantly higher response rates (60% or more) in patients with untreated advanced colorectal cancer compared to lower rates when used alone (12% to 24%).

While adding oxaliplatin to 5-FU and leucovorin improves response rates and delays tumor progression, it does not appear to extend overall survival, indicating a need for further research to understand this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of oxaliplatin in the treatment of colorectal cancer. Rothenberg, ML.[2022]

Oxaliplatin is a potent antineoplastic drug that works by blocking DNA replication and transcription, leading to cell death, and has shown greater efficacy than other platinum-based drugs like cisplatin in preclinical studies.

It is approved for treating metastatic colorectal cancer in several regions and shows promise in combination therapies with other agents, enhancing its effectiveness against various solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel combinations with oxaliplatin. Mani, S., Manalo, J., Bregman, D.[2022]

Oxaliplatin, a third-generation platinum-based chemotherapy drug, has been extensively studied in international clinical trials for its effectiveness across four different cancer indications.

Over the past decade, significant research in Japan has contributed to the understanding and evidence base for oxaliplatin, highlighting its ongoing potential in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxaliplatin -- A 10-Year Trajectory]. Kanaji, S., Oki, E., Saeki, H., et al.[2018]

The FOLFOX regimen, which includes oxaliplatin, leucovorin, and fluorouracil, demonstrated a 50% objective response rate and a median survival time of 17.4 months in a study of 23 Japanese patients with metastatic colorectal cancer.

The treatment was generally well-tolerated, with manageable side effects; while some patients experienced significant hematological toxicities, there were no treatment-related deaths, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and toxicity of FOLFOX regimen (a combination of leucovorin and fluorouracil with oxaliplatin) as first-line treatment of metastatic colorectal cancer. Matsushita, H., Tsuboi, K., Honda, I., et al.[2013]

In a study of 188 patients receiving the FOLFOX4 regimen for colorectal cancer, the relative dose intensity (RDI) of oxaliplatin decreased significantly with more treatment cycles, indicating that prolonged treatment may lead to increased side effects.

The most common adverse events affecting the feasibility of the FOLFOX4 regimen were hematologic toxicities, peripheral neuropathy, and allergic reactions, with 15.2% of patients experiencing significant peripheral neuropathy and 20.3% having allergic reactions that often required treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Relative dose intensity of FOLFOX4 regimen]. Shouji, D., Matsusaka, S., Watanabe, C., et al.[2018]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0022522320306358

A model to assess acute and delayed lung toxicity of ... Case 6 with 80 mg/L oxaliplatin demonstrated a subacute pattern of lung injury. A dose-limiting toxicity of oxaliplatin delivered by IVLP of 40 mg/L was ...

2. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/nct05611034/

In Vivo Lung Perfusion (IVLP) for Colorectal Cancer ... Participants are given oxaliplatin into one lung via IVLP and are watched very closely to see what side effects they have and to make sure the side effects are ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10921245/

Mapping the metabolic responses to oxaliplatin-based ... Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05611034/in-vivo-lung-perfusion-ivlp-for-colorectal-cancer-metastatic-to-lung

In Vivo Lung Perfusion (IVLP) for Colorectal Cancer ... This study is investigating a new technique for delivering chemotherapy directly into the lungs at the time of surgery.

5. withpower.com withpower.com/trial/phase-1-colorectal-neoplasms-9-2022-43944

IVLP with Oxaliplatin for Colorectal Cancer Spread to Lungs The median overall survival for patients receiving oxaliplatin combined with 5-FU +/- FA was 9.6 months, indicating that this treatment can provide significant ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05611034

In Vivo Lung Perfusion (IVLP) for Colorectal Cancer ... Delivering chemotherapy directly to the lungs could potentially kill any microscopic cancer cells that are present in the lungs at the time of surgery, while ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9453651/

The metabolic fate of oxaliplatin in the biological milieu ... Adjuvant chemotherapy after pulmonary metastasectomy for colorectal cancer may reduce recurrence and improve survival rates; however, ...

8. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0059485

Isolated Lung Perfusion as an Adjuvant Treatment of ... About 11% of patients suffering from colorectal cancer (CRC) will eventually develop lung metastases · The complete tumor and metastasis control has always been ...