Adaptive Radiotherapy for Head and Neck Cancer

(DEHART Trial)

Overseen By Medical College of Wisconsin Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical College of Wisconsin

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Prior malignancy, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 15

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy for advanced head and neck cancers. It uses a magnetic resonance-guided approach to adjust the radiation dose based on tumor response, potentially improving results and reducing side effects. The trial also tests atezolizumab, an immune therapy, in combination with different radiation doses. Individuals with head and neck cancer that standard therapies have not effectively treated, and who can undergo multiple MRI scans, might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that patients currently using immunosuppressive medications or those who have received certain treatments recently may not be eligible. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research has shown that radiation therapy is often used for head and neck cancer, but it can cause side effects like dry mouth, trouble swallowing, and loss of taste. These issues occur in over 90% of patients who receive this treatment. When the radiation dose exceeds 60 Gy, the risk of serious side effects can rise, affecting 5% to 15% of patients.

This trial tests different radiation doses: 50 Gy, 55 Gy, and 60 Gy. Lower doses, like 50 Gy, are generally considered safe and effective, showing good results with fewer side effects when combined with other treatments.

Atezolizumab, used with some of these radiation treatments, has been tested before and is usually well-tolerated. Most patients experience mild side effects, and no new or unexpected safety issues have been found with Atezolizumab.

As this trial is in an early phase, its main goal is to assess the safety of new treatment methods. Safety is closely monitored, especially due to the different doses and the combination with Atezolizumab. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for head and neck cancer because they explore how varying doses of radiation therapy, combined with the immune-boosting drug atezolizumab, can improve patient outcomes. Atezolizumab is an immunotherapy drug that works by blocking a protein called PD-L1, helping the immune system attack cancer more effectively. The trial also tests adaptive radiotherapy, which involves adjusting the radiation dose during treatment to better target the tumor and spare healthy tissue. This approach could lead to more personalized and effective cancer treatment strategies, potentially offering better results than traditional radiotherapy alone.

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

This trial will compare different radiation therapy doses and the addition of Atezolizumab for head and neck cancer. Studies have shown that adaptive radiotherapy, which adjusts the radiation dose based on tumor response, can improve outcomes in head and neck cancer. Participants in this trial may receive lower-dose radiation treatments, such as the 50 Gy approach, which has shown excellent survival rates of up to 92% when combined with initial chemotherapy. For those receiving the 55 Gy dose, about 70.3% of patients survived for three years, suggesting it may offer a good balance of effectiveness and safety. Although doses above 60 Gy are often used, increasing the dose beyond a certain level has not significantly improved tumor control. Research indicates that Atezolizumab has not significantly improved survival outcomes in patients with advanced head and neck cancer. Overall, adaptive radiotherapy shows promise, while the role of Atezolizumab remains less clear. ^{1 2 4 5 6}

Who Is on the Research Team?

Musaddiq J. Awan

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults aged 18+ with advanced head and neck squamous cell carcinoma, not suitable for standard chemotherapy due to age or health issues. Participants must have a specific level of organ function, no severe allergies to atezolizumab, and agree to use contraception if applicable. Excluded are those with certain recent illnesses, transplants, infections like HIV/HBV/HCV unless controlled, severe lung disease requiring oxygen therapy, or who are pregnant/breastfeeding.

Inclusion Criteria

You have experienced severe side effects from cancer treatment, as measured by the CARG toxicity score.

You have multiple chronic illnesses and your CIRS-G score is 4 or higher.

You have other medical conditions besides the one being studied, which have been evaluated using a specific tool called ACE-27, and your score is 1 or higher.

Exclusion Criteria

I have cancer spread that might cause pain or disability but hasn't yet.

I have not had major surgery in the last 28 days.

I haven't had major heart issues or strokes in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART) with concurrent atezolizumab, with radiation doses of 50 Gy, 55 Gy, or 60 Gy administered in 15 fractions over 3 weeks

3 weeks

15 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose-limiting toxicities and overall survival

12 months

What Are the Treatments Tested in This Trial?

Interventions

• 50 Gy Radiation Therapy
• 55 Gy Radiation Therapy
• 60 Gy Radiation Therapy
• Atezolizumab

Trial Overview The trial tests adaptive radiotherapy doses alongside the drug atezolizumab in patients with head and neck cancer. The radiation dose is adjusted based on tumor response using MRgRT technology—increasing where the tumor persists and decreasing where it regresses—to improve outcomes while minimizing side effects.

How Is the Trial Designed?

Group I: 60 Gray (Gy) Radiation Therapy Experimental Treatment 2 Interventions

60 Gy of ionizing radiation therapy will be administered in 15 fractions.

Group II: 55 Gray (Gy) Radiation Therapy Experimental Treatment 2 Interventions

55 Gy of ionizing radiation therapy will be administered in 15 fractions.

Group III: 50 Gray (Gy) Radiation Therapy with Concurrent Atezolizumab Experimental Treatment 2 Interventions

50 Gy of ionizing radiation therapy will be administered in 15 fractions.

Group IV: 50 Gray (Gy) Radiation Therapy Experimental Treatment 2 Interventions

50 Gy of ionizing radiation therapy will be administered in 15 fractions.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7989258/

Radiation therapy in head and neck cancer - PMC Over 90% of HNC patients who received radiotherapy suffer from xerostomia, oral discomfort, difficulty in mastication, speech and swallowing, loss of taste and ...

2. ecancer.org ecancer.org/en/news/13369-lower-dose-radiation-effective-safe-for-hpv-head-neck-cancer-after-induction-chemo

Lower-dose radiation effective, safe for HPV head & neck ... Patients who responded well to induction chemotherapy and subsequently received the lower-dose treatment experienced excellent survival - 92 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04477759

Dose-Escalated Hypofractionated Adaptive Radiotherapy ... 50 Gray (Gy) Radiation Therapy with Concurrent Atezolizumab. 50 Gy of ionizing radiation therapy will be administered in 15 fractions. Intervention/Treatment ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S245210942200032X

Head and Neck Radiation Therapy Patterns of Practice ... The first phase of this “Big Data” study aimed at characterizing variability in clinical practice patterns of dosimetric data for organs at risk (OARs)

5. redjournal.org redjournal.org/article/s0360-3016(17)30633-8/fulltext

Final Report of a Prospective Randomized Trial to Evaluate ... Increasing dose did not significantly improve tumor control, treatment package time was the only significant treatment variable, and positive surgical margins ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5605312/

Elective nodal dose of 60 Gy or 50 Gy in head and neck ... Doses of 50 Gy equivalent are sufficient to sterilize the uninvolved nodal regions because the rates of IRR are extremely low. Using ENI50 results in clinically ...