Pulmonary Suffusion for Lung Metastases

Overseen by Todd L. Demmy

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Brain metastases, Severe neuropathy, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial studies a method called pulmonary suffusion, which delivers chemotherapy directly to lung tissues. It targets patients with sarcoma or colorectal cancer that has spread to the lungs. The goal is to kill cancer cells more effectively and reduce side effects by focusing treatment on the lungs.

Will I have to stop taking my current medications?

The trial requires that you have not had chemotherapy or radiotherapy within 4 weeks before starting the study, and you must have recovered from any side effects of previous treatments. If you are currently on these treatments, you will need to stop them and wait for the specified period before joining the trial.

What data supports the effectiveness of the treatment Pulmonary Suffusion for Lung Metastases?

Research shows that cisplatin, a key component of the treatment, has been effective in treating various cancers, including esophageal cancer with liver metastasis and malignant pleural effusion in lung cancer patients. In particular, intraoperative intrapleural cisplatin has shown promise in treating carcinomatous pleuritis, suggesting potential benefits for lung metastases. ^{1 2 3 4 5}

Is Pulmonary Suffusion for Lung Metastases safe for humans?

Cisplatin, used in Pulmonary Suffusion, has been studied for safety in various conditions. It can cause side effects like nausea, vomiting, and blood-related issues, but combining it with sodium thiosulfate can reduce some toxic effects. Overall, it appears to be tolerable with careful management. ^{1 2 6 7 8}

How is the drug cisplatin used in the treatment of lung metastases unique?

Cisplatin is unique in treating lung metastases through pulmonary suffusion, which involves directly administering the drug into the pleural cavity, allowing for high local concentrations and prolonged exposure to the cancer cells, potentially increasing its effectiveness compared to systemic administration. ^{1 2 5 9 10}

Research Team

Todd L. Demmy

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for patients with sarcoma or colorectal cancer that has spread to the lungs, who can undergo a special procedure called pulmonary suffusion. They must have controlled primary tumors, be able to walk a certain distance, and not need home oxygen. Participants should agree to use contraception and not be pregnant.

Inclusion Criteria

Granulocytes > 1,500 uL

I am able to get out of my bed or chair and move around.

My primary cancer is under control as per my doctor's assessment.

Exclusion Criteria

Allergy, intolerance, or other serious reaction to chemotherapy drugs that may be used in the procedure

The investigator thinks you are not a good fit for the study drug or the way it will be given to you, based on your overall health condition.

I haven't had chemotherapy or radiotherapy in the last 4 weeks, or 6 weeks for specific drugs, and have recovered from any side effects.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo pulmonary suffusion with cisplatin and metastasectomy. Patients with unresectable sarcoma may receive additional chemotherapy 4-8 weeks post-metastasectomy.

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-ups every 3 months for the first year and then every 6 months for up to 5 years.

5 years

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Isolated Chemotherapeutic Lung Perfusion (Procedure)

Trial Overview The study tests pulmonary suffusion—a way of delivering chemotherapy directly into lung tissue—to control minimal residual disease in lung metastases from sarcoma or colorectal cancer. Cisplatin is the chemotherapeutic agent used in this minimally invasive technique.

Participant Groups

Group I: Prevention (cisplatin, metastasectomy) Experimental Treatment 3 Interventions

Patients undergo pulmonary suffusion consisting of cisplatin via infusion. Patients the undergo metastasectomy. Beginning 4-8 weeks, patients with unresectable sarcoma may receive chemotherapy.

Cisplatin is already approved in Canada, Japan for the following indications:

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Dr. Julia Faller

Roswell Park Cancer Institute

Chief Medical Officer since 2024

DO from an unspecified institution

Dr. Candace S. Johnson

Roswell Park Cancer Institute

Chief Executive Officer since 2015

PhD in Immunology from The Ohio State University

Findings from Research

Hypotonic intrapleural cisplatin (CDDP) treatment resulted in significantly higher plasma concentrations of platinum compared to isotonic treatment, suggesting enhanced drug delivery to cancer cells.

The study indicates that hypotonic CDDP is tolerable and may be beneficial for treating early pleural carcinomatosis and preventing postoperative recurrence, based on the analysis of 16 patients with varying concentrations of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of intraoperative intrapleural cisplatin chemotherapy of various osmolarities in cases of esophageal cancer. Katano, K., Tsujitani, S., Maeta, M., et al.[2013]

Instillation of cisplatin (CDDP) at a dose of 80 mg/m2 into the pleural cavity is effective for treating malignant pleural effusion, with the potential to maintain high concentrations of the drug in the pleural effusion for extended periods.

Combining CDDP with sodium thiosulfate (STS) at high doses (120-160 mg/m2) reduces hematological, renal, and auditory toxicity, although it does not alleviate nausea, vomiting, or anorexia, indicating a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Studies on an appropriate intra thoracic administration of cisplatin and sodium thiosulfate in malignant pleural effusion]. Kitajima, K., Fukuoka, M., Kusunoki, Y., et al.[2015]

Cis-dichlorodiammineplatinum(II) (CDDP) showed effectiveness in treating a patient with esophageal carcinoma and liver metastasis, resulting in a partial response after radiotherapy.

However, nephrotoxicity was noted when the total dose of CDDP reached 300 mg, indicating a need for careful monitoring of kidney function during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of cisplatin in esophageal cancer with hepatic metastasis]. Hishikawa, Y., Tanaka, S., Kawashima, T., et al.[2013]

Intraoperative intrapleural hypotonic cisplatin treatment significantly reduced the occurrence of pleural disease in non-small cell lung cancer patients, with only 14% of treated patients developing complications compared to 90% in the control group.

The treatment resulted in very low blood platinum levels, suggesting minimal systemic adverse effects, with the only noted side effect being an increase in postoperative drainage volume.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative intrapleural hypotonic cisplatin treatment for carcinomatous pleuritis. Ichinose, Y., Yano, T., Asoh, H., et al.[2019]

In a study of 32 lung cancer patients with malignant pleural effusion, intrapleural administration of OK-432 and cisplatin (CDDP) showed no significant difference in therapeutic efficacy, indicating both treatments are similarly effective.

However, OK-432 was better tolerated, causing only mild side effects like grade 1 fever and nausea, while CDDP resulted in more severe side effects, including grade 2 kidney issues and grade 3 nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of intrapleural OK-432 and cisplatin for malignant pleural effusion in lung cancer patients]. Shimizu, T., Takahashi, N., Terakado, M., et al.[2013]

In a study of 15 patients with inoperable non-small cell lung cancer, a 5-day continuous infusion of cisplatin resulted in a 40% response rate, indicating it can be an effective treatment option.

The treatment was associated with manageable side effects, including nausea and hematologic toxicity, but showed low rates of vomiting and nephrotoxicity, suggesting that this method of administration is both safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pilot phase II study of 5-day continuous infusion of cisplatin in treatment of non-small cell lung cancer]. Saito, Y., Mori, K., Yokoi, K., et al.[2013]

In a study of 111 lung cancer patients undergoing cisplatin chemotherapy, 9.9% experienced cisplatin-induced nephrotoxicity (CIN), primarily during their first course of treatment.

The study identified key risk factors for CIN, including the number of chemotherapy courses and female gender, and found that a predictive score for CIN was moderately effective in assessing risk, making it a useful tool for managing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Utility of the Predictive Score for Cisplatin-Induced Nephrotoxicity in Patients with Chemotherapy for Lung Cancer]. Sakurai, T., Takada, K., Kojima, E., et al.[2020]

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., et al.[2022]

In a study of 11 patients with malignant pleural effusion, intrapleural instillation of cisplatin led to complete disappearance of the effusion in 5 patients and significant reduction in 6 patients after four weeks, indicating its efficacy in treating this condition.

The pharmacokinetics showed that cisplatin maintained a high concentration in the pleural cavity for an extended period (half-life of 33.6 hours), which likely contributed to the positive treatment outcomes, although some patients experienced mild toxicity such as chest pain and fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Response and pharmacokinetics of cisplatin instilled into the pleural cavity]. Kudoh, S., Takifugi, N., Ryu, S., et al.[2013]

Intraperitoneal administration of cis-platinum (cDDP) showed a significant pharmacokinetic advantage, with a much higher concentration of the drug in the peritoneal cavity compared to serum, suggesting effective localized treatment for ascites caused by malignancies.

The treatment resulted in the disappearance of ascites in 10 out of 13 patients, lasting from 6 to over 135 weeks, and was generally well tolerated with no serious side effects reported, indicating both efficacy and safety of the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effective treatment of peritoneal carcinosis by intraperitoneal cis-diamminedichloroplatinum (c-DDP) administration with systemic sodium thiosulfate protection. Clinical results and pharmacokinetics]. Rückle, H., Ehninger, G., Jakob, F., et al.[2019]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of intraoperative intrapleural cisplatin chemotherapy of various osmolarities in cases of esophageal cancer. [2013]

2. Japan pubmed.ncbi.nlm.nih.gov

[Studies on an appropriate intra thoracic administration of cisplatin and sodium thiosulfate in malignant pleural effusion]. [2015]

3. Japan pubmed.ncbi.nlm.nih.gov

[Effect of cisplatin in esophageal cancer with hepatic metastasis]. [2013]

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

Intraoperative intrapleural hypotonic cisplatin treatment for carcinomatous pleuritis. [2019]

5. Japan pubmed.ncbi.nlm.nih.gov

[Comparison of intrapleural OK-432 and cisplatin for malignant pleural effusion in lung cancer patients]. [2013]

6. Japan pubmed.ncbi.nlm.nih.gov

[Pilot phase II study of 5-day continuous infusion of cisplatin in treatment of non-small cell lung cancer]. [2013]

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

[Utility of the Predictive Score for Cisplatin-Induced Nephrotoxicity in Patients with Chemotherapy for Lung Cancer]. [2020]

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

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

[Response and pharmacokinetics of cisplatin instilled into the pleural cavity]. [2013]

10. Germany pubmed.ncbi.nlm.nih.gov

[Effective treatment of peritoneal carcinosis by intraperitoneal cis-diamminedichloroplatinum (c-DDP) administration with systemic sodium thiosulfate protection. Clinical results and pharmacokinetics]. [2019]