Chemotherapy + Nivolumab for Small Cell Lung Cancer

Recruiting at 900 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

160 Participants Needed

Trial Summary

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other investigational agents or certain immunosuppressive medications, and you must not have received a live vaccine within 4 weeks before joining the trial.

What data supports the effectiveness of the drug combination of chemotherapy and Nivolumab for small cell lung cancer?

Research shows that combinations of platinum drugs like cisplatin or carboplatin with etoposide are standard treatments for small cell lung cancer, leading to median survival times of 7 to 20 months depending on the stage. These combinations have been shown to be effective, although they can have significant side effects. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs and Nivolumab safe for treating small cell lung cancer?

The combination of carboplatin and etoposide is generally well-tolerated in small cell lung cancer, with fewer side effects compared to cisplatin and etoposide. Common side effects include blood-related issues like low white blood cell counts, but serious complications are rare. ^{3 6 7 8 9}

How is the drug combination of chemotherapy and Nivolumab unique for small cell lung cancer?

This treatment combines standard chemotherapy drugs like carboplatin, cisplatin, and etoposide with Nivolumab, an immunotherapy drug that helps the immune system attack cancer cells, offering a novel approach by potentially enhancing the body's immune response against small cell lung cancer. ^{1 2 10 11 12}

What is the purpose of this trial?

This trial is testing whether adding nivolumab to standard chemotherapy improves treatment for patients with extensive stage small cell lung cancer. The chemotherapy drugs kill or stop the growth of cancer cells, while nivolumab helps the immune system attack the cancer. Nivolumab is an immunotherapy drug that has shown promise in treating various cancers, including non-small cell lung cancer and melanoma.

Research Team

Ticiana A Leal

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with extensive stage small cell lung cancer who haven't had prior treatment. They must have normal organ and marrow function, no severe allergies to monoclonal antibodies or study drugs, and not be on other investigational agents. Women of childbearing age and sexually active men must use contraception.

Inclusion Criteria

I do not have autoimmune diseases or conditions needing steroids or immunosuppressants.

I do not have lung disease causing symptoms or severe allergies to the study drug.

Patients may not be receiving any other investigational agents while on study

Exclusion Criteria

You have a positive test for hepatitis B virus or hepatitis C virus, meaning you have an active or long-lasting infection.

I have not received a live vaccine in the last 4 weeks.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive cisplatin/carboplatin and etoposide with or without nivolumab. Treatment repeats every 21 days for up to 4 cycles.

12 weeks

4 cycles, each with multiple visits for drug administration

Maintenance

Patients in Arm A continue to receive nivolumab every 2 weeks for up to 2 years.

up to 2 years

Bi-weekly visits for nivolumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up every 3 months if less than 2 years from registration, every 6 months for years 2-3, and yearly up to 5 years.

up to 5 years

Regular follow-up visits as per schedule

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Etoposide
• Nivolumab

Trial Overview The trial tests if adding Nivolumab (an immunotherapy drug) to standard chemotherapy (Cisplatin/Carboplatin and Etoposide) improves outcomes in patients with extensive stage small cell lung cancer compared to chemotherapy alone.

Participant Groups

Group I: Arm A (nivolumab, CE) Experimental Treatment 4 Interventions

Patients receive nivolumab IV over 30 minutes on day 1, carboplatin IV over 30-60 minutes on day 1 or cisplatin IV over 60-120 minutes on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients continue to receive nivolumab IV over 30 minutes every 2 weeks for up to 2 years.

Group II: Arm B (CE) Active Control 3 Interventions

Patients receive carboplatin IV over 30-60 minutes on day 1 or cisplatin IV over 60-120 minutes on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

A systematic review of 36 clinical trials found that chemotherapy regimens including cisplatin (CDDP) and/or etoposide (VP16) significantly improve survival rates in patients with small cell lung cancer (SCLC), with combined hazard ratios indicating a clear survival benefit for both drugs.

Specifically, regimens containing etoposide alone or in combination with cisplatin showed strong evidence of effectiveness, with hazard ratios of 0.72 for VP16 and 0.57 for combinations, suggesting these treatments should be prioritized in SCLC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis. Mascaux, C., Paesmans, M., Berghmans, T., et al.[2019]

Combination treatments using platinum compounds and etoposide show median survival rates of 7 to 10 months for extensive-stage and 15 to 20 months for limited-stage small cell lung cancer, indicating their effectiveness in improving patient outcomes.

Adding paclitaxel to platinum/etoposide regimens has shown promising results in early studies, with good activity and manageable toxicity, and ongoing phase III trials aim to clarify its role in enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. Hainsworth, JD., Greco, FA.[2015]

In a trial involving 228 patients with advanced non-small-cell lung cancer, cisplatin (CDDP) combined with etoposide showed a higher objective response rate (27%) compared to carboplatin (CBDCA) with etoposide (16%), although this difference was not statistically significant (P = .07).

Cisplatin treatment was associated with significantly increased toxicity, particularly myelosuppression and renal function impairment, indicating that while it may be more effective, it also poses greater risks compared to carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. Klastersky, J., Sculier, JP., Lacroix, H., et al.[2017]

In a randomized phase II trial involving 78 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of pemetrexed with carboplatin showed a median survival time of 10.4 months and a response rate of 39.5%, indicating it is an effective treatment option.

Both pemetrexed/cisplatin and pemetrexed/carboplatin combinations were well-tolerated, with manageable hematologic toxicities, suggesting that these treatments can be safely administered as first-line therapy for ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. Socinski, MA., Weissman, C., Hart, LL., et al.[2015]

Carboplatin/etoposide is an effective treatment for small cell lung cancer, showing results comparable to the traditional cisplatin/etoposide combination, although it has not been directly compared in a randomized study.

This combination has a better safety profile, particularly in elderly patients, and lacks significant nonhematologic side effects, making it suitable for further studies involving dose escalation and bone marrow transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin/etoposide in small cell lung cancer. Bishop, JF.[2018]

In a phase II trial involving 55 patients with limited-stage small cell lung cancer, the combination of paclitaxel, carboplatin, and etoposide showed promising efficacy, with 37.1% achieving a complete response and 51.4% a partial response.

The treatment was associated with moderate toxicity, primarily hematologic, but no life-threatening complications were reported, indicating that the regimen is tolerable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. Gatzemeier, U., Jagos, U., Kaukel, E., et al.[2015]

In a multicenter study involving 130 patients with advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel and carboplatin resulted in a moderate response rate of 23.8%, indicating its efficacy as a treatment option.

Both high-dose (200 mg/m2) and low-dose (175 mg/m2) paclitaxel regimens were well tolerated, with myelosuppression being the most significant side effect, but differences in toxicity between the two doses were minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). Glorieux, P., Ortmanns, P., Marien, S., et al.[2015]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis. [2019]

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

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. [2015]

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

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861. [2017]

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

Randomized phase II trial of pemetrexed combined with either cisplatin or carboplatin in untreated extensive-stage small-cell lung cancer. [2015]

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

Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Carboplatin/etoposide in small cell lung cancer. [2018]

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

Paclitaxel, carboplatin, and oral etoposide: a phase II trial in limited-stage small cell lung cancer. [2015]

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

Clinical status of carboplatin. [2013]

9. Greece pubmed.ncbi.nlm.nih.gov

Multi-center study of two dose levels of paclitaxel with carboplatin in locally advanced and metastatic non-small cell lung cancer (NSCLC). [2015]

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

Basis for experimental chemotherapy in lung cancer. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up. [2020]

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

Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer. [2017]