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

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects, safety, and effectiveness of low dose radiation to the entire body (total body irradiation \[TBI\]) and higher dose radiation to known areas of cancer (hypofractionated radiation therapy \[H-RT\]) combined with atezolizumab and chemotherapy (carboplatin \& etoposide) in treating patients with small cell lung cancer that has spread to disease sites outside of the lung (extensive stage). Extensive stage disease has historically been treated with chemotherapy alone with consideration of chest (thoracic) radiation therapy for those with response to chemotherapy, as well as consideration of preventative radiation therapy to the head (prophylactic cranial irradiation). Emerging evidence supports the synergistic interactions between immunotherapy and radiation therapy. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Combining TBI and H-RT with atezolizumab and chemotherapy may improve response to treatment.

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.

What data supports the effectiveness of the drug Atezolizumab in combination with chemotherapy for small cell lung cancer?

Research shows that adding Atezolizumab to chemotherapy significantly improves survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone, as seen in the IMpower133 trial and other studies. ^{1 2 3 4 5}

Is the combination of Atezolizumab, Carboplatin, and Etoposide safe for humans?

The combination of Atezolizumab, Carboplatin, and Etoposide has been generally well tolerated in patients with extensive-stage small cell lung cancer, with no new safety concerns beyond those known for the individual drugs. Common side effects include blood-related issues, skin rash, and low thyroid function, but it did not negatively affect patients' quality of life. ^{1 2 6 7 8}

How is the drug combination of atezolizumab, carboplatin, and etoposide unique for treating small cell lung cancer?

This drug combination is unique because it includes atezolizumab, an immune checkpoint inhibitor, which helps the immune system attack cancer cells, and is the first of its kind approved for extensive-stage small cell lung cancer. It has been shown to improve survival rates when added to the standard chemotherapy drugs carboplatin and etoposide, without worsening patients' quality of life. ^{1 3 4 9 10}

Research Team

Evan Osmundson, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Study: Atezolizumab Improves Survival in SCLC. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

4. United States 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. [2022]

5. China 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. [2022]

6. England 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. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. [2022]

9. India pubmed.ncbi.nlm.nih.gov

First-line immune-checkpoint inhibitor treatment in extensive-disease small-cell lung cancer: A classical and network meta-analysis. [2023]

10. United States 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. [2021]