Pulmonary Suffusion for Lung Metastases

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Brain metastases, Severe neuropathy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

99 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 to manage cancer that has spread there from sarcoma or colorectal cancer. The treatment uses cisplatin, a chemotherapy drug, to stop cancer cell growth by reaching them more directly, potentially avoiding the need for later, less effective treatments. This trial may suit individuals diagnosed with sarcoma or colorectal cancer that has spread to the lungs and who are physically able to undergo this treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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 prior data suggests that pulmonary suffusion is safe for treating lung metastases?

Research has shown that pulmonary suffusion, the method used in this trial to deliver cisplatin directly to lung tissues, appears safe for treating cancers that have spread. Previous studies found that this method is well-tolerated and could be a promising way to treat cancer that has metastasized to the lungs. Cisplatin, a well-known chemotherapy drug, treats various cancers, including bladder, lung, and ovarian cancers. While effective, cisplatin can cause side effects, which is common with chemotherapy. However, delivering it directly to the lungs might reduce some of the usual side effects seen with intravenous (IV) chemotherapy. This trial aims to explore the safety of this method for individuals with sarcoma or colorectal cancer that has spread to the lungs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the pulmonary suffusion technique with cisplatin for lung metastases because it offers a new delivery method that targets tumors directly in the lungs. Unlike traditional systemic chemotherapy, which circulates throughout the entire body, this method infuses cisplatin directly into the pulmonary system, potentially increasing the drug's effectiveness at the tumor site while minimizing side effects. Additionally, the approach includes a surgical procedure called metastasectomy, which could enhance outcomes by physically removing tumors after they are treated. This combination of targeted drug delivery and surgical intervention could represent a more effective and less toxic treatment option for patients with lung metastases.

What evidence suggests that pulmonary suffusion is effective for lung metastases?

Research has shown that cisplatin, which participants in this trial may receive, can help lung cancer patients live longer when used in chemotherapy. Cisplatin kills cancer cells or stops them from growing and spreading. Studies have found it to be especially effective when the cancer is detected early and completely removed. Additionally, this trial will use a method called isolated chemotherapeutic lung perfusion, such as pulmonary suffusion, to deliver drugs like cisplatin directly to the lungs. This approach can increase the impact on lung tumors while reducing side effects on the rest of the body. Early research models demonstrated a clear survival benefit using this method for treating lung cancer that has spread. ^{6 7 8 9 10}

Who Is on the Research Team?

Todd L. Demmy

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Isolated Chemotherapeutic Lung Perfusion

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.

How Is the Trial Designed?

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 European Union, United States, Canada, Japan for the following indications:

Approved in European Union 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 United States 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 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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8387576/

Evaluation of cisplatin intensity in metastatic non-small-cell ... This study does not confirm evidence of a steep clinical dose-response curve for cisplatin in NSCLC at the cisplatin dose-intensities achieved.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4982660/

Cisplatin versus carboplatin based regimens for the treatment ... We found no survival benefit to the use of cisplatin containing combination chemotherapy rather than combinations based on carboplatin.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925006288

Survival outcomes with carboplatin versus cisplatin and the ... A total of 3002 (81.8%) patients received carboplatin and 666 (18.2%) were treated with cisplatin. Patients treated with cisplatin were more ...

4. jto.org jto.org/article/S1556-0864(19)31290-0/fulltext

MA13.09 Cisplatin Sustains Lung Cancer Metastasis ... In pre-clinical models we have shown that cisplatin treatment enriches for the chemoresistant fraction of CD133+CXCR4+ lung cancer metastasis initiating cells ( ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa031644

Cisplatin-Based Adjuvant Chemotherapy in Patients with ... This large trial showed that cisplatin-based chemotherapy improves survival among patients who have undergone complete resection of non–small-cell lung cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4146684/

Cisplatin in cancer therapy: molecular mechanisms of action It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers.

7. reference.medscape.com reference.medscape.com/drug/platinol-aq-cisplatin-342108

Cisplatin dosing, indications, interactions, adverse effects, ... Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may ...

8. go.drugbank.com go.drugbank.com/drugs/DB00515

Cisplatin: Uses, Interactions, Mechanism of Action Cisplatin is a platinum based chemotherapy agent used to treat various sarcomas, carcinomas, lymphomas, and germ cell tumors.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427383/

Preliminary Analyses of Phase I Safety and Drug Delivery ... Conclusions: Suffusion for metastatic malignancies appears safe and warrants further investigation. 1. Introduction. The second most common ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT06896890

Cisplatin (CIS) Administered As Dry Powder for Inhalation ... This study may provide insights into whether this add-on treatment might be a safe and potentially efficacious option for NSCLC patients. Detailed Description.