Total Body Irradiation + Atezolizumab + Chemotherapy for Small Cell Lung Cancer

(TESSERACT Trial)

Overseen By Vanderbilt-Ingram Services for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vanderbilt-Ingram Cancer Center

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: Cardiovascular disease, Hypertension, Autoimmune, others

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

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

Compensation: Varies

Number of Visits: 19

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat small cell lung cancer that has spread beyond the lungs. Researchers combine low-dose radiation to the whole body with higher-dose radiation to specific cancer areas, alongside an immune-boosting drug (atezolizumab, also known as Tecentriq) and chemotherapy (carboplatin and etoposide). The goal is to determine if this combination is safe and more effective than traditional treatments. The trial seeks participants with extensive-stage small cell lung cancer that cannot be treated with regular radiation and who experience symptoms impacting daily life. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, certain medications like antivirals for hepatitis B and some immunosuppressive drugs are not allowed. It's best to discuss your specific medications with the study team.

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

Studies have shown that combining atezolizumab with chemotherapy is generally safe for patients with extensive-stage small cell lung cancer (ES-SCLC). Research suggests that this combination can significantly improve survival rates, and patients have typically handled the treatment well in past studies.

Carboplatin, an important part of this treatment, is similar to another cancer drug called cisplatin but may be gentler on the body. Research has found that carboplatin is commonly used and is a popular choice for treating small cell lung cancer.

Etoposide, another drug in the trial, has been effective in slowing down tumor growth. While it may not cure the cancer, it helps manage it.

Total body irradiation (TBI) and hypofractionated radiation therapy (H-RT) are also included in the treatment. Studies have shown that radiation therapy can improve survival in small cell lung cancer patients. Hypofractionated radiation, where larger doses are given fewer times, has been found safe and effective in other studies.

Overall, past research has shown promise for the combination of these treatments. Each part of the treatment has been used before and is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for small cell lung cancer because it combines several powerful therapies in a novel way. Unlike standard treatments, which often rely solely on chemotherapy, this approach integrates atezolizumab, an immunotherapy drug that helps the immune system target cancer cells more effectively. Additionally, the use of total body irradiation (TBI) and hyperfractionated radiation therapy (H-RT) aims to enhance the overall effectiveness by delivering radiation in a more precise manner. This combination has the potential to improve outcomes by attacking the cancer on multiple fronts, which is a significant advancement over traditional single-modality treatments.

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

In this trial, participants will receive a combination of treatments, including atezolizumab, carboplatin, etoposide, total body irradiation (TBI), and hypofractionated radiation therapy (H-RT). Research has shown that adding atezolizumab to chemotherapy helps patients with extensive-stage small cell lung cancer (ES-SCLC) live longer. Specifically, one study found that patients who received atezolizumab with chemotherapy lived an average of 12.3 months, longer than those who did not receive it. Using carboplatin with etoposide has also improved survival rates for these patients. Etoposide plays a crucial role in chemotherapy treatments and has shown good results. Additionally, combining radiation therapy with these treatments might enhance the body's ability to fight cancer, as radiation works well with immunotherapy like atezolizumab. Overall, evidence suggests that this combination of treatments may be more effective for treating small cell lung cancer that has spread. ^{2 3 4 5 6}

Who Is on the Research Team?

Evan Osmundson, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

Adults with extensive stage small-cell lung cancer who haven't had prior treatment for it can join. They must be in decent physical shape (ECOG 0-2), not have severe infections or major recent surgeries, and agree to use birth control. People with certain heart conditions, uncontrolled symptoms, or a history of severe allergies to similar drugs cannot participate.

Inclusion Criteria

You do not have hepatitis B.

I have brain metastases but am managing the symptoms.

My doctor thinks I am a good candidate for immunotherapy.

Exclusion Criteria

Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months of the last dose of Atezolizumab

Treatment with investigational therapy within 28 days prior to initiation of study treatment

I am currently taking medication that weakens my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive carboplatin and atezolizumab IV on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles. Patients also receive TBI BID on day 18 or 19 of cycle 1 and H-RT daily over 7 days.

12 weeks

4 cycles, multiple visits per cycle

Maintenance

Patients receive atezolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for 12 cycles.

36 weeks

12 cycles, 1 visit per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs within 30 days and then every 3-4 months for up to 3 years.

Up to 3 years

Regular follow-up visits every 3-4 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Carboplatin
• Etoposide
• Hypofractionated Radiation Therapy
• Total Body Irradiation

Trial Overview The trial is testing if adding total body irradiation and targeted high-dose radiation to the standard atezolizumab plus chemotherapy regimen improves outcomes for patients with extensive stage small-cell lung cancer. It's looking at safety and how well this combination works together.

How Is the Trial Designed?

Group I: Treatment (carboplatin, atezolizumab, etoposide, TBI, H-RT) Experimental Treatment 6 Interventions

Description INDUCTION PHASE: Patients receive carboplatin IV and atezolizumab IV on day 1 of each cycle and etoposide IV on days 1-3 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive TBI BID on day 18 or 19 of cycle 1 and beginning 2-3 days later, H-RT daily over 7 days in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive atezolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout the trial.

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?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

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 phase 3 trial with 572 patients, atezolizumab significantly improved overall survival by 7.1 months compared to platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC) and high PD-L1 expression (20.2 months vs. 13.1 months).

Atezolizumab also demonstrated a favorable safety profile, with fewer grade 3 or 4 adverse events (30.1%) compared to chemotherapy (52.5%), indicating it may be a safer first-line treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. Herbst, RS., Giaccone, G., de Marinis, F., et al.[2022]

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]

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 significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

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]

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 study of 225 patients with extensive-stage small-cell lung cancer, those treated with atezolizumab combined with etoposide/platinum (EP) had a longer progression-free survival (PFS) of 7.10 months compared to 6.50 months for those receiving EP alone, indicating enhanced efficacy of the combination treatment.

The most common adverse event in the atezolizumab group was bone marrow suppression (58.6%), with immune-related adverse events occurring in 14.3% of patients, suggesting that while atezolizumab improves outcomes, it also carries a risk of significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of atezolizumab in combination with etoposide/platinum for treatment of extensive-stage small-cell lung cancer: A real-world, multicenter, retrospective, controlled study in China. Chen, H., Ma, X., Liu, J., et al.[2022]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Citations

1. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of extensive SCLC. IFCT-1905 CLINATEZO studied consecutive patients receiving ...

5. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life More patients lived longer with TECENTRIQ + chemotherapy ... Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11880126/

Efficacy and safety analysis of atezolizumab continuation ... The IMpower 133 trial demonstrated that combining atezolizumab with chemotherapy significantly enhanced survival, establishing chemo-immunotherapy as the ...