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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of high-dose radiation therapy (SBRT) and the immunotherapy atezolizumab (Tecentriq) to determine its safety in people with certain types of advanced cancer. The goal is to see if this combination can shrink large tumors in patients who have not responded to standard treatments. Individuals diagnosed with metastatic cancer that did not respond to previous treatments might be eligible to join. 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 novel combination therapy.

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.

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

A previous study found the combination of atezolizumab and a specific type of radiation therapy called SBRT to be safe, with only three patients experiencing significant side effects. Other research shows that most patients handled the treatment well, with many experiencing stable disease or some improvement. This suggests that the combination is generally well-tolerated in people with certain types of cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining high-dose radiation with atezolizumab immunotherapy for cancer because this approach brings a fresh angle to treatment. While standard cancer therapies like chemotherapy and traditional radiation aim to directly kill cancer cells, this combination leverages the immune system. Atezolizumab, an immune checkpoint inhibitor, helps the body's own defenses recognize and attack cancer cells more effectively. When paired with Stereotactic Ablative Radiotherapy (SBRT), a precise and intense form of radiation, there's potential not only for enhanced cancer control but also for sparking a stronger immune response throughout the body. This synergy could lead to more effective treatments with potentially fewer side effects compared to conventional methods.

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

This trial will evaluate the combination of atezolizumab, a drug that boosts the immune system, with stereotactic ablative radiotherapy (SBRT), a precise, high-dose radiation treatment. Research has shown that this combination may help treat certain cancers. In one study, 24% of patients experienced a partial response, with their tumors shrinking, and 57% had stable disease, with no cancer progression. Atezolizumab helps the immune system attack cancer cells, while SBRT targets tumors with focused radiation. Together, these treatments might improve outcomes for patients with advanced cancer who have few other options. Early evidence suggests this combination is safe and could help control cancer growth. ^{1 2 3 5 6}

Who Is on the Research Team?

Gregory Gan, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10474145/

Atezolizumab plus stereotactic ablative radiotherapy for ... The authors report the results of a phase I study testing the addition of atezolizumab (anti-PD-L1) to SABR in high risk, medically inoperable, early-stage, ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625004468

Atezolizumab and Stereotactic Body Radiation in ... The best overall response was a partial response in 5 (24%) and stable disease in 12 (57%) patients. The median duration of response was 8.6 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02599454

NCT02599454 | Atezolizumab and Stereotactic Body ... Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37658083/

Atezolizumab plus stereotactic ablative radiotherapy for ... We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.9011

Atezolizumab plus stereotactic ablative therapy for ... Atezolizumab plus SABR is feasible, safe and shows an efficacy signal in medically inoperable early stage NSCLC.

6. febs.onlinelibrary.wiley.com febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13330

Atezolizumab and stereotactic body radiotherapy in patients ... We found the combined treatment to be safe with grade 3 toxicity reported in three patients. As the best overall response, four patients had a ...