Lamivudine + Chemoimmunotherapy for Small Cell Lung Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Symptomatic brain metastasis, Leptomeningeal involvement, Active infections, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for small cell lung cancer that has spread and become resistant to standard therapies. Researchers aim to determine if adding lamivudine, an antiviral drug, to the usual chemoimmunotherapy can stop the cancer from growing and spreading. The trial includes drugs like carboplatin, etoposide, and atezolizumab (Tecentriq), which work together to attack cancer cells in different ways. People with extensively spread small cell lung cancer who have not seen disease progression on prior platinum-based treatments might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to benefit from innovative therapies.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the study team to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lamivudine, a pill used to fight viruses, is generally safe. It is often used to treat hepatitis B, allowing for long-term use without problems. However, this does not guarantee the same effectiveness for cancer treatment.

Studies have found that atezolizumab, a drug that helps the immune system fight cancer, is also safe. It is often used with chemotherapy for lung cancer and is usually well-tolerated, though it can cause side effects like tiredness and nausea.

Carboplatin and etoposide are two chemotherapy drugs used in this trial. They are common treatments for small cell lung cancer. Research suggests they are generally safe, but they can cause side effects like low blood counts and nausea. These drugs have been used for many years and are a standard part of cancer treatment.

This trial is in an early stage, so researchers are closely monitoring the safety of these drugs. However, they have been used safely in other treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about this treatment because it introduces lamivudine, typically known as an antiviral drug for HIV, into the mix for small cell lung cancer. Unlike standard treatments like carboplatin and etoposide, which focus on directly attacking cancer cells, lamivudine might alter the immune environment, potentially helping the body better target the cancer. Plus, combining lamivudine with atezolizumab, an immunotherapy drug, could enhance the body's immune response against the cancer. This novel approach is what makes the treatment stand out and why researchers are eager to see if it offers improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that adding atezolizumab to standard chemotherapy, such as carboplatin and etoposide, helps small cell lung cancer patients live longer. Atezolizumab enhances the immune system's ability to fight cancer. Studies have found that this combination leads to better outcomes and delays cancer progression. In this trial, participants will receive lamivudine alongside chemoimmunotherapy with atezolizumab, carboplatin, and etoposide. Lamivudine, an antiviral drug, might help prevent the cancer from becoming resistant to these treatments. Although primarily used for viral infections, it may stop cancer cells from resisting the drugs. Overall, these treatments together show promise in managing extensive-stage small cell lung cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Grace Dy, MD

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

Adults with extensive stage small cell lung cancer who have measurable disease, acceptable organ function, and an ECOG performance status of 0 or 1. They may have had one cycle of chemoimmunotherapy but no more than one prior line of platinum-based treatment at least a year ago without progression during that treatment. Participants must not be HIV positive or have certain other health conditions.

Inclusion Criteria

Your liver enzymes (ALT and AST) are not more than 3 times the upper limit of normal. If you have cancer that has spread to your liver, it's okay if your liver enzymes are not more than 5 times the upper limit of normal.

I have had only one round of platinum-based chemotherapy for small cell lung cancer.

My lung cancer diagnosis was confirmed through lab tests.

Exclusion Criteria

I have a condition that weakens my immune system, such as HIV/AIDS.

I haven't had a heart attack or blood clot in the last 6 months, and I don't have severe heart disease.

I have not had an autoimmune disorder requiring immunosuppressants in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive lamivudine orally once daily and chemoimmunotherapy including carboplatin, atezolizumab, and etoposide. Treatment repeats every 28 days for up to 4 cycles.

16 weeks

Maintenance

Patients continue to receive lamivudine orally once daily and atezolizumab intravenously. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs 30 days after treatment and then every 60 days thereafter.

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• Lamivudine

Trial Overview

The trial is testing the effectiveness of adding lamivudine to standard chemoimmunotherapy (carboplatin, etoposide, and atezolizumab) for treating extensive stage small cell lung cancer. The goal is to see if lamivudine can help prevent the tumor from becoming resistant to therapy.

How Is the Trial Designed?

Group I: Treatment (lamivudine, chemoimmunotherapy) Experimental Treatment 4 Interventions

INDUCTION: Patients receive lamivudine PO QD on days 1-28. Patients also receive carboplatin IV over 30-60 minutes and atezolizumab IV on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lamivudine PO QD on days 1-28 and atezolizumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: Patients who are not eligible for atezolizumab as outlined in exclusion criteria or who refuse to receive atezolizumab may still be treated in this study with carboplatin and etoposide as the IV drug component, in addition to lamivudine orally administered.

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

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

In a study of 518 patients with extensive small cell lung cancer (SCLC) receiving atezolizumab plus chemotherapy, the median overall survival was 11.3 months, with 46.7% of patients alive at 12 months, indicating the treatment's effectiveness in a real-world setting.

The study demonstrated that 23.6% of patients continued atezolizumab treatment beyond disease progression, suggesting a potential strategy for improving outcomes, particularly in patients with better performance status (PS 0/1) who had a median overall survival of 12.2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Falchero, L., Guisier, F., Darrason, M., et al.[2023]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

A phase III trial involving 77 patients with small cell lung cancer is evaluating the efficacy and safety of gemcitabine combined with carboplatin compared to the standard cisplatin and etoposide regimen.

Preliminary results suggest that gemcitabine/carboplatin has a lower incidence of severe side effects compared to cisplatin/etoposide, making it a potentially safer treatment option for patients with extensive-stage and poor-prognosis small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation. Steele, JP.[2022]

The FDA approved atezolizumab, a PD-L1 inhibitor, in combination with carboplatin and etoposide as a first-line treatment for small cell lung cancer, highlighting its role in enhancing therapy options.

This approval was supported by the phase III IMpower133 trial, which demonstrated that the addition of atezolizumab significantly improved both overall survival and progression-free survival in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Atezolizumab OK'd for SCLC. [2020]

A phase I trial presented in 2015 indicates that rovalpituzumab tesirine, an experimental antibody-drug conjugate, shows potential effectiveness against recurrent small cell lung cancer, a type of cancer with limited treatment options.

This trial highlights the promise of rovalpituzumab tesirine as a new therapeutic approach for patients suffering from this challenging form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ADC Shows Effectiveness in SCLC. [2015]

An 80-year-old male with extensive-stage small cell lung cancer safely received a combination of carboplatin, etoposide, and atezolizumab while undergoing hemodialysis, indicating that this treatment can be feasible for patients with similar conditions.

Despite experiencing grade 4 neutropenia and leukopenia during the first cycle, the patient was able to continue treatment with adjusted dosages, and no severe non-haematological adverse events were reported after four cycles, demonstrating a positive response to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature. Imaji, M., Fujimoto, D., Kato, M., et al.[2021]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 65 patients with extensive-disease small-cell lung cancer, the combination of atezolizumab, carboplatin, and etoposide showed a high response rate of 73.8%, with 80.5% in elderly patients (median age 74 years).

Despite some significant hematological toxicities, such as decreased neutrophil counts in 61.1% of elderly patients, the treatment demonstrated acceptable safety and efficacy, suggesting it could be a preferred standard treatment for elderly patients with this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data of atezolizumab plus carboplatin and etoposide in elderly patients with extensive-disease small-cell lung cancer. Shiono, A., Imai, H., Wasamoto, S., et al.[2023]

The combination of anti-PD1/PD-L1 immunotherapy with chemotherapy (carboplatin plus etoposide) significantly improves overall survival in patients with extensive-disease small-cell lung cancer (ED-SCLC), with a hazard ratio of 0.746 indicating a 25% reduction in the risk of death compared to chemotherapy alone.

Among various treatment combinations, nivolumab plus chemotherapy was identified as the most effective option for improving both overall survival and progression-free survival, outperforming the anti-CTLA-4 approach in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis. Mutlu, H., Bozcuk, H., Artaç, M., et al.[2023]

In a study of 124 patients with treatment-naïve, metastatic nonsquamous PD-L1-positive non-small cell lung cancer, the combination of atezolizumab with carboplatin and nab-paclitaxel showed significantly improved overall survival (19.9 months) and progression-free survival (8.5 months) compared to carboplatin and nab-paclitaxel alone (14.8 months and 5.1 months, respectively).

While the combination therapy had a higher incidence of manageable adverse events like neutropenia and anemia, it still demonstrated a tolerable safety profile, suggesting it could be an effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and nab-paclitaxel chemotherapy with or without atezolizumab as front-line management for treatment-naïve metastatic nonsquamous non-small cell lung cancer with PD-L1 staining: a retrospective study. Xu, B., Cheng, H., Li, K., et al.[2023]

Atezolizumab combined with carboplatin and etoposide was effective in treating a 75-year-old woman with advanced small cell lung cancer and an ECOG Performance Status of 2, leading to complete regression after 4 cycles of treatment.

Despite experiencing some adverse effects like anemia and thrombocytopenia, the patient's therapy was continued due to positive imaging results, highlighting the potential for immunochemotherapy in patients typically excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. Dębczyński, M., Mojsak, D., Kuklińska, B., et al.[2022]

In a long-term follow-up of patients with metastatic urothelial carcinoma (mUC) who had previously undergone platinum-based chemotherapy, atezolizumab showed a 24-month overall survival (OS) rate of 23%, compared to 13% for those receiving chemotherapy, indicating a potential for durable remission.

Patients treated with atezolizumab experienced fewer severe treatment-related adverse events (43% for chemotherapy vs. 22% for atezolizumab), suggesting a better safety profile, although atezolizumab was associated with more mild adverse events of special interest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Versus Chemotherapy in Patients with Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: A Long-term Overall Survival and Safety Update from the Phase 3 IMvigor211 Clinical Trial. van der Heijden, MS., Loriot, Y., Durán, I., et al.[2022]

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