Radiotherapy + Durvalumab for Squamous Cell Carcinoma

No longer recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Autoimmune disorders, Active infection, 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: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety of combining Durvalumab, an immune-boosting drug, with focused radiation therapy for certain types of head and neck cancers. It targets individuals with specific cancers in the oral cavity, larynx, hypopharynx, or oropharynx who are eligible for surgery. Participants should have cancer that hasn't spread to distant parts of the body and be willing to undergo surgery after the trial treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting the trial, except for certain low-dose steroids. 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 has shown that durvalumab, a drug used in many cancer treatments, is generally safe. It often works well with other cancer drugs, and most patients do not experience major problems. When combined with stereotactic body radiation therapy (SBRT), the treatment is also well-tolerated.

Studies indicate that combining SBRT with durvalumab does not cause severe side effects for most people. However, some patients might experience mild to moderate issues, such as fatigue or skin reactions, which are common with these types of treatments.

Although this trial is in the early stages, previous research on durvalumab and SBRT suggests it is reasonably safe. The treatment is expected to be safe, but researchers will closely monitor participants to ensure their well-being. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for squamous cell carcinoma because it combines Durvalumab, an immune checkpoint inhibitor, with Stereotactic Body Radiation Therapy (SBRT). Durvalumab works by blocking the PD-L1 protein, which can help the immune system detect and attack cancer cells more effectively. SBRT delivers high doses of radiation with precision, minimizing damage to surrounding healthy tissues. This combination could potentially enhance the effectiveness of treatment by both boosting the body's immune response and directly targeting the tumor, offering a promising alternative to standard treatments like surgery and conventional radiation.

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

Studies have shown that durvalumab, a drug that helps the immune system recognize and attack cancer cells, provides lasting anti-tumor effects in patients with head and neck cancer. This suggests it may enhance the body's defenses against cancer. In this trial, participants will receive durvalumab combined with Stereotactic Body Radiation Therapy (SBRT), a precise radiation treatment effective for various cancers, including those in the head and neck. Research indicates that SBRT can lead to high survival rates, making it a promising treatment. Together, these treatments aim to boost the body's ability to fight cancer and accurately target tumors. ^{1 6 7 8 9}

Who Is on the Research Team?

Sana D. Karam

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults over 18 with certain types of head and neck cancer (oral cavity, larynx, hypopharynx, or HPV-negative oropharynx) that can be surgically removed. They should not have had prior treatment with PD1/PD-L1 inhibitors and must be able to follow the study protocol.

Inclusion Criteria

I am older than 18 years.

I am considered a good candidate for surgery by my ENT surgeon and I am willing to undergo surgery.

Your hemoglobin level must be at least 9.0 grams per deciliter (g/dL).

Exclusion Criteria

I have had cancer before, but it meets the trial's exceptions.

I have had cancer spread to the lining of my brain and spinal cord.

History of active primary immunodeficiency

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive one dose of neoadjuvant durvalumab 1500 mg concurrently with the first dose of radiation (RT) over approximately one week

1 week

2 visits (in-person)

Surgical Resection

Participants undergo standard of care surgery approximately 3-6 weeks after radiation

3-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Standard of Care Therapy
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The trial is testing Durvalumab in combination with Stereotactic Body Radiation Therapy before surgery against the standard care for specific head and neck cancers. It's a single-arm phase I/Ib safety trial across multiple centers.

How Is the Trial Designed?

Group I: Dose Escalation and Expansion Experimental Treatment 3 Interventions

Part 1 of this trial will use a traditional 3+3 design will be used for this trial (i.e. cohort sizes of 3 patients for the first and second cohort at each dose level). Dose escalation will occur as long as there are minimal dose limiting toxicities.The expectation is that 9 patients will be enrolled to the trial during part 1.This is based on the expectation that all dose levels are safe (i.e. patients will not experience DLTs at all dose levels). The range of patients needed will be 6-12 patients. Part 2 of this trial will be an expansion cohort. A total of 8 additional patients will be enrolled at the dose level determined to be the MTD in part 1 of the study. These 8 patients will be used to confirm that the MTD is a safe combination, as well as provide additional patients to investigate the efficacy for the treatment combination. Note: Standard of care surgery will follow 3-6 weeks after medication and radiation treatment.

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?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

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

Published Research Related to This Trial

In a study of 107 patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT), the median progression-free survival (PFS) was 20.7 months, indicating effective treatment outcomes.

Factors associated with longer PFS included a favorable response to CCRT, a radiation dose of 62 Gy or more, and having stage IIIA NSCLC, while shorter durations of durvalumab treatment and lower radiation doses were linked to increased mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. Takeda, Y., Kusaba, Y., Tsukita, Y., et al.[2022]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

This Phase II study (DOLPHIN) is investigating the safety and efficacy of durvalumab combined with radiation therapy in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) who are PD-L1 positive and unable to undergo chemotherapy, aiming for improved outcomes without the adverse effects of chemotherapy.

The primary goal is to evaluate the 12-month progression-free survival rate, with secondary goals including overall survival and safety, highlighting the potential of combining immunotherapy and radiotherapy for better treatment options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design for a Multicenter, Phase II Study of Durvalumab Plus Concurrent Radiation Therapy in Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Study (WJOG11619L). Tachihara, M., Tsujino, K., Ishihara, T., et al.[2021]

In a study of 924 patients with unresectable stage III non-small cell lung cancer treated with durvalumab, race did not significantly affect treatment patterns such as initiation delays, interruptions, or discontinuations.

Black patients experienced fewer immune-related adverse events and pneumonitis compared to White patients, suggesting potential differences in safety profiles between racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. Moore, AM., Nooruddin, Z., Reveles, KR., et al.[2023]

In a study involving 10 patients receiving palliative radiotherapy (RT) combined with durvalumab, the treatment was well tolerated, with only 50% experiencing mild to moderate adverse events, primarily G2 mucositis, and no severe adverse events reported.

The treatment showed promising efficacy, with a 60% objective response rate in evaluable lesions and a significant decrease in tumor growth rate after RT, indicating that durvalumab combined with RT may effectively reduce tumor size in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Levy, A., Massard, C., Soria, JC., et al.[2022]

In a study of 68 patients with locally advanced non-small cell lung cancer treated with intensity-modulated radiotherapy (IMRT), the administration of durvalumab significantly improved distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), with hazard ratios of 0.31, 0.33, and 0.32 respectively.

The study also found that while grade 2 or higher radiation pneumonitis (RP) was associated with worse DMFS, reducing the incidence of RP could enhance patient outcomes, highlighting the importance of managing treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. Yamamoto, T., Tsukita, Y., Katagiri, Y., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Here, we report a meta-analysis investigating the safety and efficacy of durvalumab (MEDI4736), an inhibitor of PD-L1, in various solid tumors.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01693562

NCT01693562 | A Phase 1/2 Study to Evaluate MEDI4736 Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer. 2019 Mar ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0959804919300073

Safety and efficacy of durvalumab in patients with head ... Durvalumab monotherapy was safe in previously treated recurrent/metastatic head and neck squamous cell carcinoma. Durable antitumour responses were observed.

4. researchgate.net researchgate.net/publication/313341968_Updated_safety_and_efficacy_of_durvalumab_MEDI4736_an_anti-PD-L_1_antibody_in_patients_from_a_squamous_cell_carcinoma_of_the_head_and_neck_SCCHN_expansion_cohort

Updated safety and efficacy of durvalumab (MEDI4736), an ... In a phase 1/2 study to evaluate durvalumab, 11 an ORR of 11% was achieved with durvalumab monotherapy; in the Phase II Study of Durvalumab ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10342070/

A Phase Ib Study of Durvalumab (MEDI4736) in ... Even in patients with tumor diameters > 6 cm, we have shown a five-year LC rate of 70% for cervical squamous cell carcinoma [13]. Wakatsuki et al. reported a ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03618134

Stereotactic Body Radiation Therapy and Durvalumab With ... This phase Ib/II trial studies the side effects and how well stereotactic body radiation therapy and durvalumab with or without tremelimumab before surgery work

7. journals.sagepub.com journals.sagepub.com/doi/full/10.1089/thy.2022.0050

A Pilot Study of Durvalumab (MEDI4736) with ... Metastatic anaplastic thyroid cancer (ATC) has a poor prognosis. This pilot study aims to evaluate tremelimumab plus durvalumab with stereotactic body ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT345553

Outcomes and safety analysis of a phase IB trial ... Outcomes and safety analysis of a phase IB trial of stereotactic body radiotherapy (SBRT) to all sites of oligometastatic non-small cell lung cancer combined ...

9. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03148327/

Clinical Trial: NCT03148327 It is hoped that we will learn more about the basic safety and science of durvalumab (MEDI 4736) combined with Stereotactic Ablative Body ...