SBRT + Immunotherapy for Head and Neck Squamous Cell Carcinoma

Not currently recruiting at 3 trial locations

Overseen By Diane Trudel, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Nasopharyngeal carcinoma, Autoimmune disorders, 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: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two immunotherapy drugs, Durvalumab (Imfinzi) and Tremelimumab, with a precise radiotherapy called SBRT. The goal is to determine if this combination can control the spread of head and neck cancers that have metastasized. Individuals diagnosed with head and neck cancer that has spread beyond the original site and have up to 10 treatable cancer spots may be suitable for this trial. As a Phase 1, Phase 2 trial, the research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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

The trial protocol does not clearly specify if you need to stop taking your current medications. However, you cannot be on any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment, and there are restrictions on immunosuppressive medications and recent live vaccines. It's best to discuss your specific medications with the study team.

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

Research shows that combining Durvalumab and Tremelimumab with Stereotactic Body Radiotherapy (SBRT) has been studied for safety in treating head and neck cancer. Previous studies found this combination to be generally well-tolerated. Some patients experienced side effects, but most were manageable. Common issues included fatigue and mild skin reactions, while serious side effects were less common.

In other studies, both Durvalumab and Tremelimumab have been used alone or together to treat various types of cancer, demonstrating a reasonable safety profile, meaning they don't cause severe problems for most people. Since this trial is in the early stages, it primarily focuses on ensuring the treatment's safety. Researchers closely monitor any side effects to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for head and neck squamous cell carcinoma because it combines two immunotherapy drugs, durvalumab and tremelimumab, with SBRT (stereotactic body radiation therapy) for a potentially more powerful effect. Unlike traditional chemotherapy or radiation alone, this approach seeks to harness and amplify the body's immune response against cancer cells. The combination of these two drugs with SBRT might enhance the precision and effectiveness of treatment, offering hope for better control of the disease with potentially fewer side effects.

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

Research has shown that immunotherapy drugs like durvalumab and tremelimumab, which target the PD-1/PD-L1 pathway, effectively treat advanced head and neck cancers. These drugs assist the immune system in combating cancer cells, slowing disease progression. In this trial, participants will receive a combination of durvalumab and tremelimumab with Stereotactic Body Radiotherapy (SBRT). SBRT uses precise radiation to destroy cancer cells and may enhance the effectiveness of these drugs by releasing cancer cell fragments that further activate the immune system. Early results suggest that this combination might extend patient survival and potentially control cancer growth better than current treatments alone. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with metastatic head and neck squamous cell carcinoma who have a good performance status, functioning organs, and marrow. They must not be pregnant or breastfeeding and agree to use birth control. Those with up to four prior systemic therapies are eligible but cannot have brain metastases, uncontrolled illnesses, or recent major surgeries.

Inclusion Criteria

ECOG/WHO performance status score of ≤ 1

Adequate normal organ and marrow function

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients

Exclusion Criteria

You have a severe, ongoing health issue that is not being managed or controlled.

You have cancer that has spread to your brain or spinal cord.

You have received a live vaccine within 30 days before the first dose of the study medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab and Tremelimumab every 4 weeks for 4 doses, with SBRT administered between cycle 2 and 3, completed within a 3-week period

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• SBRT
• Tremelimumab

Trial Overview The study tests the combination of Durvalumab (MEDI4736) and Tremelimumab immunotherapies with SBRT (a precise radiation therapy). It aims to see if this combo can better control cancer progression in patients by using the body's immune system alongside targeted radiation.

How Is the Trial Designed?

Group I: Durvalumab + tremelimumab and SBRT Experimental Treatment 3 Interventions

All subjects will receive durvalumab (1500 mg IV q4week) and tremelimumab (75mg q4week) for 4 doses, followed by durvalumab alone (1500 mg IV q4week) until disease progression, unacceptable toxicity or patient withdrawal. SBRT will be administered between cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9293682/

A Pilot Study of Durvalumab (MEDI4736) with ... This pilot study aims to evaluate tremelimumab plus durvalumab with stereotactic body radiotherapy (SBRT) to improve overall survival (OS).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6332607/

Phase I/II trial of Durvalumab plus Tremelimumab and ... The efficacy of immunotherapy targeting the PD-1/PD-L1 pathway has previously been demonstrated in metastatic head and neck squamous cell ...

3. journals.sagepub.com journals.sagepub.com/doi/abs/10.1089/thy.2022.0050

A Pilot Study of Durvalumab (MEDI4736) with ... Eligible patients received up to 4 doses tremelimumab (75 mg) given q4 weeks and up to 1 year of durvalumab (1500 mg) given q4 weeks. SBRT at 9 Gy × 3 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02369874

NCT02369874 | Study of MEDI4736 Monotherapy and in ... The main objectives of the study are to: assess the efficacy of MEDI4736 + tremelimumab combination therapy versus SoC in patients with squamous cell carcinoma ...

5. researchgate.net researchgate.net/publication/360425618_A_Pilot_Study_of_Durvalumab_MEDI4736_with_Tremelimumab_in_Combination_with_Image_Guided_Stereotactic_Body_Radiotherapy_SBRT_in_the_Treatment_of_Metastatic_Anaplastic_Thyroid_Cancer?_tp=eyJjb250ZXh0Ijp7InBhZ2UiOiJzY2llbnRpZmljQ29udHJpYnV0aW9ucyIsInByZXZpb3VzUGFnZSI6bnVsbCwic3ViUGFnZSI6bnVsbH19

A Pilot Study of Durvalumab (MEDI4736) with ... In a pilot study, [24] 13 ATC patients received tremelimumab plus durvalumab with stereotactic body radiotherapy. However, only 1 patient had ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02262741

NCT02262741 | A Phase I Study to Evaluate the Safety, ... A Phase I Study to Evaluate the Safety, Tolerability and Efficacy of MEDI4736 (Durvalumab) With Tremelimumab in Head and Neck Cancer.

7. researchgate.net researchgate.net/publication/283979112_Phase_II_randomized_open-label_study_of_durvalumab_MEDI4736_or_tremelimumab_monotherapy_or_durvalumab_tremelimumab_in_patients_with_recurrent_or_metastatic_RM_squamous_cell_carcinoma_of_the_head_and_n

Phase II, randomized, open-label study of durvalumab ... A multicenter phase IB study assessing the combination of durvalumab and tremelimumab in non-small cell lung cancer reported 23% objective ...