Radiotherapy + Durvalumab for Squamous Cell Carcinoma

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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multi-center, prospective, single-arm phase I/Ib safety trial. Patients eligible for treatment must be diagnosed with non-metastatic, biopsy-proven stage II-IVB oral cavity, stage III-IVB larynx and hypopharynx, or stage III-IVB HPV/p16 negative intermediate-high risk oropharynx head and neck cancer, and must be eligible and amenable to surgical resection.

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.

What data supports the effectiveness of the drug Durvalumab when used with radiotherapy for Squamous Cell Carcinoma?

Research shows that Durvalumab, when used after radiotherapy, has been effective in improving survival outcomes in patients with non-small cell lung cancer (NSCLC) who are not eligible for chemotherapy. This suggests that combining Durvalumab with radiotherapy could potentially offer similar benefits for other cancers, like Squamous Cell Carcinoma. ^{1 2 3 4 5}

Is the combination of radiotherapy and Durvalumab safe for humans?

Studies have shown that Durvalumab, when used with radiotherapy, is generally safe for patients with certain types of lung cancer, although some patients may experience side effects that prevent them from completing treatment. The safety of this combination is being actively studied, and it is important for participants to discuss potential risks with their healthcare provider. ^{1 2 6 7 8}

How is the treatment of radiotherapy combined with durvalumab unique for squamous cell carcinoma?

This treatment is unique because it combines radiotherapy with durvalumab, an immune therapy that helps the body's immune system attack cancer cells, potentially offering better survival outcomes compared to radiotherapy alone, especially for patients who cannot undergo chemotherapy. ^{1 2 3 4 9}

Research Team

Sana D. Karam

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]

2. Ireland 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. [2022]

3. China pubmed.ncbi.nlm.nih.gov

Durvalumab after concurrent chemoradiotherapy in a patient with chemotherapy-resistant unresectable stage III non-small cell lung cancer: a case report. [2021]

4. England 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. [2022]

5. England 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. [2022]

6. New Zealand 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). [2021]

7. England 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report. [2021]

9. England pubmed.ncbi.nlm.nih.gov

A phase 2 trial of durvalumab treatment following radiation monotherapy in patients with non-small cell lung cancer ineligible for stage III chemoradiotherapy: The SPIRAL-RT study. [2023]