Inhaled Gemcitabine for Cancer with Lung Spread

Overseen By Najat C. Daw-Bitar, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Bronchodilators, Corticosteroids

Disqualifiers: Pregnancy, Active asthma, Cardiac disease, 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: 3

Duration: 4 weeks per cycle, up to 12 cycles

44 Participants Needed

Trial Summary

What is the purpose of this trial?

Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential participant. The goal of this clinical research study is to find the highest tolerable dose of gemcitabine that can be given by inhalation (breathing it as a mist) to patients with solid tumors that have spread to the lungs from other parts of the body. The safety and side effects of this drug will also be studied. This is an investigational study. Gemcitabine is FDA approved and commercially available for the treatment of pancreatic and lung cancer, and other solid tumors. Its administration by inhalation is investigational. The study doctor can explain how the study drug is designed to work. Up to 44 participants will be enrolled in this study. All will take part at MD Anderson.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently being treated with bronchodilators, corticosteroids, or other cancer therapies like chemotherapy or immunotherapy.

What data supports the effectiveness of the drug Gemcitabine (Gemzar) for cancer with lung spread?

Gemcitabine (Gemzar) has shown effectiveness in treating non-small cell lung cancer (NSCLC), with studies reporting a tumor regression rate of about 20% when used alone and a response rate over 60% when combined with cisplatin. It is considered safe and active for advanced NSCLC, suggesting potential benefits for cancers that have spread to the lungs. ^{1 2 3 4 5}

Is inhaled gemcitabine safe for humans?

Gemcitabine has been used safely in humans for various cancers, but it can cause side effects like low blood cell counts, nausea, and lung injury. Serious lung injury is rare but has been reported, especially in patients with existing lung conditions. ^{6 7 8 9 10}

What makes inhaled gemcitabine unique for treating cancer with lung spread?

Inhaled gemcitabine is unique because it is administered directly into the lungs, which may allow for higher concentrations of the drug to reach the cancerous areas with potentially fewer side effects compared to traditional intravenous methods. This approach is different from standard treatments that typically involve systemic administration, such as intravenous gemcitabine combined with other drugs like cisplatin. ^{4 11 12 13 14}

Research Team

Najat C. Daw-Bitar, MD

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

This trial is for patients aged 12-50 with solid tumors that have spread to the lungs, where no curative or life-prolonging treatments are suitable. Participants must be willing to follow the study's procedures and have good organ function. They can't join if they're using bronchodilators/corticosteroids, have uncontrolled illnesses, are pregnant/breastfeeding, or suffer from certain symptoms like fever or cough.

Inclusion Criteria

I am between 12 and 50 years old.

I have previously received GCB treatment.

I am willing to follow the study's treatment plan and safety checks.

Exclusion Criteria

I do not have any severe illnesses or social situations that would prevent me from following the study's requirements.

Pregnant or breastfeeding women will not be entered into this study due to risks of fetal and teratogenic adverse events as seen in animal studies

I am not currently receiving any cancer treatments like chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive aerosol gemcitabine by mist 2 times each week for 4 weeks per cycle, with dose escalation to determine the maximum tolerated dose

4 weeks per cycle, up to 12 cycles

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including phone calls every 3 months

Up to 30 days after last dose

Phone calls every 3 months

End of Dosing Visit

Final assessments including physical exam, blood tests, PFTs, and CT scan within 30 days of last dose

Within 30 days of last dose

Treatment Details

Interventions

• Gemcitabine

Trial Overview The study aims to determine the highest dose of gemcitabine that can be safely inhaled by patients with lung metastases from other cancers. All participants will receive this treatment at MD Anderson Cancer Center, and up to 44 individuals will take part.

Participant Groups

Group I: Aerosol Gemcitabine (GCB) Experimental Treatment 1 Intervention

Dose Escalation Cohort: Participants take Gemcitabine by mist 2 times each week for 4 weeks (28 days). Expansion Cohort: Participants with OS lung metastases receive study drug at the maximum tolerated dose from Dose Escalation Cohort. Participants may continue to receive the study drug for up to 12 cycles per decision of doctor.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

James B. and Lois R. Archer Charitable Foundation

Collaborator

Trials

1

Recruited

40+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Findings from Research

In a large phase II study involving 161 patients with non-small cell lung cancer, gemcitabine showed an objective response rate of 21.8% and a median survival of 9.4 months, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, suggesting that gemcitabine is a safe and active agent for patients with advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent gemcitabine in non-small cell lung cancer: the French experience. Le Chevalier, T., Gottfried, M.[2022]

Gemcitabine, along with other third-generation therapies, is now commonly used in various stages of non-small-cell lung cancer (NSCLC), from early-stage to metastatic disease, but the overall response rate in advanced cases remains around 30% with a median survival of 10 months.

There is a need for improved treatment strategies, including the combination of gemcitabine with targeted agents like anti-angiogenic agents or EGFR inhibitors, to enhance efficacy in NSCLC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gemcitabine and non small-cell lung cancer]. Vignot, S., Besse, B.[2022]

Neoadjuvant chemotherapy, particularly the gemcitabine/cisplatin regimen, has shown promising results in improving overall survival for patients with stage IIIA N2 non-small-cell lung cancer (NSCLC), with a twofold increase in survival compared to surgery alone based on multiple phase II trials.

Preliminary results from five phase II trials indicate that this chemotherapy combination has a response rate greater than 60% and is generally well tolerated, although some patients experienced thrombocytopenia, leading to dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung cancer. Scagliotti, GV.[2022]

Gemcitabine, a nucleoside analogue, shows promise in treating non-small cell lung cancer (NSCLC) and has been evaluated in economic studies across multiple countries, indicating it may be cost-effective compared to other treatments.

The economic evaluations suggest that gemcitabine can be administered safely in an outpatient setting with a lower side-effect profile, which contributes to its potential cost savings in NSCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. Minshall, ME., Liepa, AM.[2022]

Gemcitabine is a highly valuable chemotherapeutic agent for treating both early and advanced non-small cell lung cancer (NSCLC), showing a tumor regression rate of about 20% in patients, regardless of their previous chemotherapy history.

It is particularly effective in combination with platinum-based therapies and can be safely administered alongside radiotherapy, making it a key component in multimodal treatment strategies for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine (Gemzar) in non-small cell lung cancer. Manegold, C.[2022]

A total of 178 cases of severe lung injury associated with gemcitabine were identified, with significant occurrences reported in clinical trials and spontaneous reports, highlighting the need for awareness among healthcare providers.

The incidence of gemcitabine-associated lung injury was notably high (up to 42%) in patients receiving gemcitabine in combination with other lung-injury-inducing therapies, such as bleomycin, indicating a potential risk factor for this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical features and correlates of gemcitabine-associated lung injury: findings from the RADAR project. Belknap, SM., Kuzel, TM., Yarnold, PR., et al.[2022]

In a phase II study involving 69 patients with advanced non-small cell lung cancer (NSCLC), gemcitabine showed an overall response rate of 20.9% and a median survival time of 9.0 months, indicating its efficacy as a treatment option.

While gemcitabine was found to be effective, it also caused significant side effects, with 22.7% of patients experiencing severe neutropenia and other serious toxicities like septic shock and interstitial pneumonia in a few cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of gemcitabine in the treatment of patients with non-small cell lung cancer: a multicenter phase II study. Yokoyama, A., Nakai, Y., Yoneda, S., et al.[2022]

A study of 162 patients with non-small cell lung cancer (NSCLC) treated with gemcitabine showed that it has good tolerability, with severe side effects occurring infrequently and no patient deaths during chemotherapy.

The most common side effects were gastrointestinal issues like nausea and vomiting, while more serious effects like leukopenia and thrombocytopenia were observed only in later treatment cycles, suggesting gemcitabine could be a viable first-line therapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer. Gallelli, L., Nardi, M., Prantera, T., et al.[2022]

Gemcitabine (GEMZAR) has shown to be an effective treatment for non-small-cell lung cancer (NSCLC) with a response rate of about 21% as a single agent, and it has a mild toxicity profile, making it suitable for combination therapies.

When combined with cisplatin, gemcitabine achieved higher response rates ranging from 38% to 54% and median survival times of 8.4 to 14.3 months, with manageable side effects, indicating its potential as a preferred treatment option in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. Steward, WP.[2022]

Gemcitabine, while effective for treating pancreatic and biliary tract cancers, can cause severe lung injury, as evidenced by seven reported cases in patients averaging 71 years old, with a male-to-female ratio of 5:2.

In these cases, all patients experienced significant adverse lung effects, with three fatalities linked to the lung injury, highlighting the need for careful monitoring of respiratory health in patients receiving gemcitabine, especially those with pre-existing lung conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Seven cases of gemcitabine-induced lung injury during treatment for pancreatic or biliary tract cancers]. Tsumura, T., Matsuo, H., Maruo, T., et al.[2022]

In a phase II study involving 50 patients with unresectable malignant mesothelioma, the combination of gemcitabine and cisplatin showed a modest overall response rate of 12%, with one complete response and five partial responses, primarily in patients with specific tumor histologies.

The treatment resulted in a median overall survival of 10 months and a median progression-free survival of 6 months, with an acceptable safety profile, although 16 patients experienced Grade 4 toxicities, mainly hematologic, and there were no treatment-related deaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin in unresectable malignant mesothelioma of the pleura: a phase II study of the Southwest Oncology Group (SWOG 9810). Kalmadi, SR., Rankin, C., Kraut, MJ., et al.[2022]

Gemcitabine was initially approved for treating advanced non-small-cell lung cancer (NSCLC) in combination with cisplatin, but research has shifted towards combining it with newer drugs that may offer better efficacy and fewer side effects.

The article reviews the effectiveness of non-cisplatin-based combinations of gemcitabine with other agents, highlighting the ongoing evolution in treatment strategies for advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative. Cappuzzo, F., Rocha Lima, CM., Sherman, CA., et al.[2022]

Gemcitabine, in combination with carboplatin, has shown promise in managing a case of advanced non-small cell lung cancer (NSCLC), indicating potential efficacy for this treatment protocol.

The report includes clinical status updates and findings from electron bronchoscopy, suggesting that this combination therapy may be worth further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gemcitabine in the treatment of advanced non-small cell lung cancer: report of one case]. Liu, AH., Wang, XS., Zhou, Y., et al.[2022]

Gemcitabine has shown good tolerance and effectiveness in treating non-small-cell lung cancer, achieving response rates of 30% to 60% when used in combination with radiation therapy.

In a phase III trial involving 187 patients with unresectable stage III non-small-cell lung cancer, the combination of gemcitabine and cisplatin as induction therapy led to a median survival of 18 months and a median progression-free survival of 10 months, demonstrating its efficacy without compromising the safety of concurrent radiation treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing chemoradiation in locally advanced non-small-cell lung cancer. Curran, WJ., Choy, H.[2022]

References

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

Single-agent gemcitabine in non-small cell lung cancer: the French experience. [2022]

2. France pubmed.ncbi.nlm.nih.gov

[Gemcitabine and non small-cell lung cancer]. [2022]

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

Gemcitabine/cisplatin as induction therapy for stage IIIA N2 non-small-cell lung cancer. [2022]

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

Review of the pharmacoeconomic research on gemcitabine in the treatment of advanced non-small cell lung cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Gemcitabine (Gemzar) in non-small cell lung cancer. [2022]

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

Clinical features and correlates of gemcitabine-associated lung injury: findings from the RADAR project. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Activity of gemcitabine in the treatment of patients with non-small cell lung cancer: a multicenter phase II study. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Retrospective analysis of adverse drug reactions induced by gemcitabine treatment in patients with non-small cell lung cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Combination studies with gemcitabine in the treatment of non-small-cell lung cancer. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

[Seven cases of gemcitabine-induced lung injury during treatment for pancreatic or biliary tract cancers]. [2022]

11. Ireland pubmed.ncbi.nlm.nih.gov

Gemcitabine and cisplatin in unresectable malignant mesothelioma of the pleura: a phase II study of the Southwest Oncology Group (SWOG 9810). [2022]

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

Advances in treatment of inoperable NSCLC: gemcitabine doublets--a promising alternative. [2022]

13. China pubmed.ncbi.nlm.nih.gov

[Gemcitabine in the treatment of advanced non-small cell lung cancer: report of one case]. [2022]

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

Optimizing chemoradiation in locally advanced non-small-cell lung cancer. [2022]