Radiotherapy + Atezolizumab for Head and Neck Cancer

No longer recruiting at 3 trial locations

Overseen By Tessa McSpadden

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, PD-1/PD-L1 inhibitors

Disqualifiers: Active infection, Autoimmune disease, Cardiovascular disease, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining radiation therapy with atezolizumab for individuals with specific types of head and neck cancer. Atezolizumab, a form of immunotherapy, assists the immune system in combating cancer. The study includes surgery followed by additional radiation, with or without chemotherapy, according to national guidelines. This trial is suitable for individuals with stage II-IVB head and neck cancer who have been advised by their doctor that surgery is an option. As a Phase 1 trial, the research focuses on understanding the treatment's effects in participants, offering them the opportunity to be among the first to receive this innovative therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like immunosuppressive drugs and some cancer therapies must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that atezolizumab, a cancer treatment drug, is generally safe for patients. In studies involving individuals with advanced head and neck cancer, most patients tolerated atezolizumab well. While most experienced some side effects, no new safety issues emerged. These side effects occurred in about 91-95% of patients but were usually manageable.

Stereotactic Body Radiation Therapy (SBRT), a precise radiation treatment, also has a strong safety record. Serious side effects from SBRT are rare, affecting less than 10% of patients. This treatment is favored for its ability to effectively target tumors while minimizing damage to nearby healthy tissue.

Both atezolizumab and SBRT have undergone safety testing in people with head and neck cancer. Although side effects are common, they are usually not severe, and both treatments are considered to have manageable safety profiles. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which typically involve surgery, chemotherapy, or conventional radiation therapy, atezolizumab offers a novel approach by using immunotherapy. Atezolizumab is a checkpoint inhibitor that works differently by unleashing the body's immune system to target and attack cancer cells more effectively. When combined with stereotactic body radiation therapy (SBRT), which delivers precise, high doses of radiation, it has the potential to enhance the immune response and improve treatment outcomes. Researchers are excited about this combination because it could potentially lead to more effective and less invasive treatment options for patients with head and neck cancer.

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

Research has shown that stereotactic body radiation therapy (SBRT) can be effective for head and neck cancers, with studies finding a 1-year survival rate of up to 75.9%. This treatment precisely targets high doses directly at the cancer, helping to protect healthy tissues. In this trial, some participants will receive SBRT combined with the drug atezolizumab, which has shown mixed results in improving survival for these cancers. Some studies report promising outcomes with atezolizumab, while others did not find significant improvements. This trial explores whether combining SBRT and atezolizumab could offer better results. ^{2 3 4 6 7}

Who Is on the Research Team?

Sana Karam, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults over 18 with certain advanced head and neck cancers (excluding HPV-related types) who can undergo radiation, atezolizumab treatment, and surgery. They must be in good health otherwise, not have had recent major surgeries or severe infections, and cannot be on immunosuppressive drugs or have a history of significant other diseases.

Inclusion Criteria

My blood thinner medication dose has been stable.

Hemoglobin ≥9.0 g/dL

Provision to sign and date the consent form

Exclusion Criteria

Patients with QTc interval > 470 msec during screening

I have not had a severe infection or been hospitalized for one in the last 4 weeks.

Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy with Neoadjuvant Atezolizumab

Participants receive neoadjuvant atezolizumab with 3 fractions of SBRT

3 weeks

3 visits (in-person)

Surgical Resection

Participants undergo surgical resection following radiotherapy and atezolizumab

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Stereotactic Body Radiation Therapy

Trial Overview

The trial is testing the effectiveness of combining radiotherapy with atezolizumab before surgical removal of the cancer. It aims to see how well patients do after this combined treatment followed by standard post-surgery care which may include chemotherapy.

How Is the Trial Designed?

Group I: SBRT with Neoadjuvant Atezolizumab Experimental Treatment 2 Interventions

After the MTD is determined, additional patients will be enrolled at this dose level to ensure 14 patients evaluable for the efficacy endpoints (MPR) at the planned interim analysis. The 6 patients treated at the MTD in phase I will be included if evaluable for MPR, so that additional 8 patients will be enrolled in this stage.

Group II: Phase 1 Lead-in SBRT with Neoadjuvant Atezolizumab Experimental Treatment 2 Interventions

Initially 3 patients will be enrolled to receive one dose of neoadjuvant atezolizumab with 3 fractions of 8 Gy SBRT (dose level 2, i.e. starting dose). If there are \< = 1 DLT related to the neoadjuvant therapy, another 3 patients will be enrolled at the same SBRT dose with only one cycle of neoadjuvant atezolizumab. And if there are \<= 1 DLT out of the 6 patients, then determine MTD at this dose level.

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 Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

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

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40079944/

Atezolizumab in High-Risk Locally Advanced Squamous ...

In this study, atezolizumab did not improve clinical outcomes in patients with LA SCCHN at high risk of disease progression after multimodal definitive ...

2.

appliedclinicaltrialsonline.com

appliedclinicaltrialsonline.com/view/tecentriq-imvoke010-trial-head-neck-cancer

Tecentriq Falls Short of Primary Endpoint in IMvoke010 ...

Phase III IMvoke010 trial found that maintenance treatment with Tecentriq (atezolizumab) did not significantly improve survival compared ...

3.

onclive.com

onclive.com/view/atezolizumab-fails-to-improve-survival-outcomes-after-definitive-local-therapy-in-high-risk-hnscc

Atezolizumab Fails to Improve Survival Outcomes After ...

Administration of atezolizumab after definitive local therapy did not improve EFS or OS in patients with head and neck squamous cell carcinoma.

4.

jamanetwork.com

jamanetwork.com/journals/jama/article-abstract/2831624

Atezolizumab in High-Risk Locally Advanced Squamous ...

There was no difference in overall survival between atezolizumab and placebo (24-month overall survival, 82.0% vs 79.2%, respectively). No new ...

5.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)31889-7/fulltext

Safety and clinical activity of atezolizumab in head and ...

With an encouraging 1-year overall survival rate of 36%, atezolizumab's efficacy appears to be in the same range as other programmed death-ligand 1/programmed ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30219915/

Safety and clinical activity of atezolizumab in head and ...

In this heavily pre-treated advanced HNC cohort, atezolizumab had a tolerable safety profile and encouraging activity, with responses ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0923753419318897

Safety and clinical activity of atezolizumab in head and ...

With an encouraging 1-year overall survival rate of 36%, atezolizumab's efficacy appears to be in the same range as other programmed death-ligand 1/programmed ...