High-Dose Radiation + Immunotherapy for Cancer

Overseen By Maggie Thomas

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Kansas Medical Center

Must not be taking: Antineoplastics, Immunosuppressants

Disqualifiers: Pregnancy, Severe infection, 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: 1

Duration: 1-2 weeks

54 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine whether cytoreduction of bulky metastatic disease using ultra high dose SBRT in combination with immunotherapy is tolerable and feasible In patients who have exhausted SoC treatment options.

Do I need to stop my current medications for the trial?

Yes, you will need to stop your current systemic therapy medications. There is a required washout period (time without taking certain medications) of 5 elimination half-lives or 28 days, whichever is longer, before starting the study treatment.

What data supports the effectiveness of the treatment Atezolizumab, Tecentriq, and Stereotactic Ablative Radiotherapy (SBRT) for cancer?

Research shows that combining atezolizumab (an immune system-boosting drug) with stereotactic ablative radiotherapy (a precise form of radiation therapy) can improve outcomes in certain lung cancers, with early responses seen in some patients. Additionally, combining atezolizumab with chemotherapy has been shown to improve outcomes in advanced small cell lung cancer, suggesting potential benefits when combined with radiotherapy. ^{1 2 3 4 5}

Is the combination of high-dose radiation and immunotherapy safe for humans?

The combination of high-dose radiation (SABR) and the immunotherapy drug atezolizumab has been shown to be well tolerated in a phase I trial for early-stage non-small cell lung cancer, with the full dose of atezolizumab being the maximum tolerated dose. Additionally, a similar combination with pembrolizumab has demonstrated safety in patients with advanced solid tumors. ^{1 3 4 6 7}

How does the treatment of high-dose radiation and atezolizumab differ from other cancer treatments?

This treatment combines high-dose radiation with atezolizumab, an immune therapy that helps the body's immune system attack cancer cells. It is unique because it uses a combination of precise radiation and an immune-boosting drug to potentially improve outcomes for patients who cannot undergo surgery, offering a new approach compared to traditional chemotherapy or surgery alone. ^{1 3 6 8 9}

Research Team

Gregory Gan, MD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

This trial is for adults with metastatic cancer who have tried at least one line of systemic therapy or immunotherapy without success. They must have a large enough lesion, good organ function, and no active severe infections or immune disorders. Pregnant women and those planning to become pregnant soon cannot participate.

Inclusion Criteria

My organ function tests are within normal ranges.

I have a tumor that is at least 65 cc in size.

Ability of participant to understand this study, and participant willingness to sign a written informed consent

Exclusion Criteria

I am not planning to use other cancer treatments during this study.

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

I have not had a severe infection in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive ultra-high dose SBRT over 3-5 fractions within 1-2 weeks with concurrent and adjuvant atezolizumab immunotherapy

1-2 weeks

Multiple visits (in-person) for SBRT fractions

Immunotherapy

Participants receive atezolizumab (1680 mg on Day 1 of each 28-day cycle) for up to one year

Up to 12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular follow-up visits

Treatment Details

Interventions

• Atezolizumab
• Stereotactic Ablative Radiotherapy (SBRT)

Trial Overview The study tests the combination of ultra-high dose Stereotactic Ablative Radiotherapy (SBRT) with the immunotherapy drug Atezolizumab in patients with bulky metastatic disease who've exhausted standard treatments. It aims to see if this approach is safe and doable.

Participant Groups

Group I: SBRT with concurrent and adjuvant atezolizumab immunotherapy Experimental Treatment 2 Interventions

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?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Findings from Research

In a phase I study involving 20 patients with early-stage non-small cell lung cancer, the combination of stereotactic ablative radiotherapy (SABR) and the immune-checkpoint inhibitor atezolizumab was well tolerated, with the maximum tolerated dose established at 1200 mg.

Early efficacy signals were observed, with 17% of patients showing responses after two cycles of atezolizumab before starting SABR, and specific biomarkers indicating T cell activation were found to be predictive of treatment benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. Monjazeb, AM., Daly, ME., Luxardi, G., et al.[2023]

The TREASURE trial is a phase II clinical study involving 104 patients with extensive disease small cell lung cancer (SCLC) to evaluate the effectiveness of adding thoracic radiotherapy (TRT) to atezolizumab maintenance therapy after initial chemo-immunotherapy, with overall survival as the primary endpoint.

This trial aims to enhance treatment outcomes by exploring the synergistic effects of combining immunotherapy with radiotherapy, while also assessing safety and collecting biomarker samples for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. Bozorgmehr, F., Christopoulos, P., Chung, I., et al.[2022]

In a phase 2 study involving 45 patients with invasive bladder cancer, the combination of radiation therapy and atezolizumab resulted in a high pathologic complete response (pCR) rate of 84.4%, particularly in older patients and those with high PD-L1 expression.

The treatment was associated with acceptable toxicity, with 93.3% of patients experiencing adverse events, mostly mild to moderate, and only 13.3% experiencing grade 3 adverse events, indicating that this approach could be a viable bladder-preserving option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. Kimura, T., Ishikawa, H., Nagumo, Y., et al.[2023]

In a phase I trial involving 38 patients with extensive-stage small cell lung cancer, the combination of pembrolizumab and thoracic radiotherapy was found to be safe, with no dose-limiting toxicities observed in the first 35 days of treatment.

The median progression-free survival was 6.1 months and overall survival was 8.4 months, suggesting that while the safety profile is promising, further studies are needed to fully understand the efficacy of this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. Welsh, JW., Heymach, JV., Chen, D., et al.[2023]

The ESPERa trial is designed to evaluate the efficacy and safety of adding Stereotactic Body Radiotherapy (SBRT) to pembrolizumab-pemetrexed maintenance therapy in advanced non-small cell lung cancer (NSCLC) patients who have shown a response or stability after initial treatment, with the primary goal of improving progression-free survival (PFS).

Preliminary data suggest that combining immunotherapy with radiotherapy is safe and effective, but the systematic integration of these treatments in first-line therapy for NSCLC is still under investigation, highlighting the potential for SBRT to enhance treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Design and Rationale for Espera Trial: A Multicentre, Randomized, Phase II Clinical Trial Evaluating the Potential Efficacy of Adding SBRT to Pembrolizumab-Pemetrexed Maintenance in Responsive or Stable Advanced Non-Squamous NSCLC After Chemo-Immunotherapy Induction. Belluomini, L., Dionisi, V., Palmerio, S., et al.[2022]

In a study of 68 patients with advanced solid tumors, the combination of stereotactic body radiotherapy (SBRT) followed by pembrolizumab showed a high one-year treated metastasis control rate of 89.5%, indicating effective tumor response regardless of whether the tumors received complete or partial radiation coverage.

The study found that treated metastasis control (TMC) was significantly associated with improved overall survival, and SBRT altered tumor gene expression by increasing immune-related genes while decreasing those related to cell cycle and DNA repair, suggesting a mechanism for enhanced immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

The combination of stereotactic body radiotherapy (SBRT) and pembrolizumab (SBRT+P) is safe for patients with large, advanced solid tumors, with only 7.2% experiencing dose-limiting toxicities in a study involving 97 patients.

Patients who showed a positive response to SBRT+P had significantly better overall survival rates, with a 1-year overall survival of 71% for responders, compared to 0% for nonresponders, highlighting the potential efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases. Korpics, MC., Onderdonk, BE., Dadey, RE., et al.[2023]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease - a randomized, open-label, multicenter phase II trial. [2022]

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

Efficacy and Safety of Bladder Preservation Therapy in Combination with Atezolizumab and Radiation Therapy (BPT-ART) for Invasive Bladder Cancer: Interim Analysis from a Multicenter, Open-label, Prospective Phase 2 Trial. [2023]

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

Phase I Trial of Pembrolizumab and Radiation Therapy after Induction Chemotherapy for Extensive-Stage Small Cell Lung Cancer. [2023]

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

Study Design and Rationale for Espera Trial: A Multicentre, Randomized, Phase II Clinical Trial Evaluating the Potential Efficacy of Adding SBRT to Pembrolizumab-Pemetrexed Maintenance in Responsive or Stable Advanced Non-Squamous NSCLC After Chemo-Immunotherapy Induction. [2022]

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

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. [2021]

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

Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases. [2023]

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

Atezolizumab: First Global Approval. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Bladder preservation therapy in combination with atezolizumab and radiation therapy for invasive bladder cancer (BPT-ART) - A study protocol for an open-label, phase II, multicenter study. [2021]