IVLP with Oxaliplatin for Colorectal Cancer Spread to Lungs

Overseen by Marcelo Cypel, MD MSc

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. ^{1 2 3 4 5}

Is 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. ^{2 3 5 6 7}

How 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. ^{1 2 3 5 8}

Research Team

Marcelo Cypel, MD MSc

Principal Investigator

University Health Network, Toronto

Eligibility 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.

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.

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

Treatment Details

Interventions

• Oxaliplatin (Alkylating agents)

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.

Participant Groups

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+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Findings from Research

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]

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]

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]

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]

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]

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, 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Novel combinations with oxaliplatin. [2022]

2. England 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. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Oxaliplatin: a review of its use in combination therapy for advanced metastatic colorectal cancer. [2022]

4. Japan 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. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Management of allergic reactions to oxaliplatin in colorectal cancer patients. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

[Relative dose intensity of FOLFOX4 regimen]. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

[Oxaliplatin -- A 10-Year Trajectory]. [2018]