Durvalumab + Radiotherapy for Oral Cancer

Recruiting at 2 trial locations

Overseen By Lori Stravers

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Active infection, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 9 weeks

18 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop taking your current medications. However, you cannot be on certain treatments like chemotherapy or immunosuppressive drugs. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Durvalumab when used with radiotherapy for oral cancer?

Durvalumab, when used with radiotherapy, has shown promising results in treating head and neck cancers, which are similar to oral cancers. In other studies, Durvalumab has improved survival rates in lung cancer patients, suggesting it may also be effective in other cancers. ^{1 2 3 4 5}

Is the combination of Durvalumab and Radiotherapy safe for humans?

Durvalumab, when used with radiotherapy, has been studied in patients with lung cancer, and some people experienced side effects that prevented them from continuing treatment. However, these studies suggest that the combination can be used safely in many patients, although individual reactions can vary. ^{1 6 7 8 9}

How is the treatment of Durvalumab combined with Intensity Modulated Radiotherapy unique for oral cancer?

This treatment is unique because it combines durvalumab, an immune therapy that helps the body's immune system attack cancer cells, with intensity-modulated radiotherapy (IMRT), which precisely targets cancer cells while sparing healthy tissue. This combination aims to enhance the effectiveness of treatment by using the body's own defenses alongside advanced radiation techniques. ^{1 2 4 10 11}

What is the purpose of this trial?

The purpose of this study is to investigate other drugs that may be combined with radiation to treat cancer. The study focuses on determining whether a combination of durvalumab with radiation can both improve cure rate and at the same time have less serious side effects. Throughout this document, this investigational drug will be referred to as the "study drug", or named individually (durvalumab). The study drug in this research is referred to as investigational because the U.S. Food and Drug Administration (FDA) has not yet approved itfor the treatment of head and neck cancer. Durvalumab was FDA approved in 2017 for the treatment of certain types of bladder cancer, but has not been approved for use in Head and Neck cancer patients. Durvalumab is an experimental drug that uses the body's immune system to fight the cancer. This study drug is being used in other ongoing clinical trials for other types of cancers. The doctor feels that a patient may experience fewer side effects using this study drug with radiation rather than using cisplatin. The doctor is also investigating whether using this drug can increase the effectiveness of treatment.

Research Team

Siddharth Sheth, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

Adults over 18 with intermediate-risk head and neck cancer who've had surgery but no prior treatment for the tumor. They must be in good health, have a performance status of 0 or 1, and women must not be pregnant and agree to contraception. People can't join if they're on other cancer treatments, have an allergy to durvalumab, are immunosuppressed, have certain infections like HIV or hepatitis B/C, or autoimmune diseases.

Inclusion Criteria

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information. Consent for the use of any residual material from biopsy (archival tissue) and serial blood draws will be required for enrollment

WOCBP must be willing to abstain from heterosexual activity or to use at least 1 highly effective method of contraception from the time of informed consent until 90 days after durvalumab monotherapy treatment is discontinued

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Treatment with any investigational drug within 28 days or 5 half-lives of Day 1 of treatment on this study, whichever is shortest

My cancer has spread to other parts of my body.

I am currently undergoing treatment with chemotherapy, investigational drugs, or hormone therapy for cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab and radiation therapy during cycles 1-3, with radiation therapy administered daily over 6 weeks

9 weeks

Daily visits for radiation therapy (Mon-Fri) during the first 6 weeks

Extended Treatment

Participants continue to receive durvalumab only during cycles 4-6

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up for up to 5 years or until death

5 years

Treatment Details

Interventions

• Durvalumab
• Intensity Modulated Radiotherapy Treatments

Trial Overview The trial is testing whether combining durvalumab (an immune system-boosting drug) with intensity-modulated radiotherapy improves cure rates while causing fewer side effects than traditional treatments for head and neck cancers. Durvalumab isn't yet approved for this type of cancer but has been used in bladder cancer.

Participant Groups

Group I: Open-label, single-arm Experimental Treatment 2 Interventions

Durvalumab in combination with intensity modulated radiotherapy (IMRT) treatments

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

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

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 1006 patients with stage III non-small cell lung cancer (NSCLC), early discontinuation of adjuvant durvalumab therapy was common, primarily due to tumor progression and immune-related adverse events, highlighting the need for careful monitoring during treatment.

The analysis indicated that shorter durations of durvalumab (6 or 9 months) may provide similar progression-free survival compared to the full 12-month course, suggesting that optimizing treatment duration could balance efficacy and patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. Bryant, AK., Sankar, K., Zhao, L., et al.[2023]

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 of 104 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with driver variations experienced significantly shorter progression-free survival (PFS) times (8.4 months) compared to those without driver variations (40.1 months), indicating that these mutations may limit the effectiveness of the PACIFIC regimen.

Despite the shorter PFS, there was no significant difference in overall survival (OS) between patients with and without driver variations, suggesting that while the initial treatment may be less effective for some, it does not necessarily impact long-term survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Driver Oncogene Variations With Outcomes in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Consolidative Durvalumab. Liu, Y., Zhang, Z., Rinsurongkawong, W., et al.[2023]

In a Phase II trial involving 74 patients with unresectable, locally advanced non-small cell lung cancer (NSCLC), durvalumab immunotherapy combined with radiotherapy resulted in a promising 12-month progression-free survival (PFS) rate of 72.1%, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with a high objective response rate of 90.9%, although 52.9% of patients experienced severe adverse events (grade 3 or 4), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. Tachihara, M., Tsujino, K., Ishihara, T., et al.[2023]

The DEDALUS phase 2 trial is investigating a new treatment approach for 45 patients with unresectable stage III non-small cell lung cancer (NSCLC), combining induction chemo-immunotherapy with de-intensified radiotherapy and the immunotherapy drug durvalumab.

The primary focus of the study is to assess safety by monitoring severe adverse events within 6 months, while secondary goals include evaluating progression-free survival (PFS) and overall survival (OS), indicating a comprehensive approach to understanding both the safety and effectiveness of this treatment regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial. Filippi, AR., Agustoni, F., Arcangeli, S., et al.[2023]

Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who received concurrent chemoradiotherapy (CCRT) and durvalumab had a significantly higher 1-year local control rate (89%) compared to those who received CCRT alone (47%), indicating that adding durvalumab may enhance local tumor control.

While the addition of durvalumab improved local control, it was associated with a slightly higher incidence of grade 2 pneumonitis (50% in the durvalumab cohort vs. 41% in the CCRT-alone cohort), highlighting the importance of monitoring for respiratory side effects in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Efficacy and Toxicity of Concurrent Chemoradiotherapy and Durvalumab and Concurrent Chemoradiotherapy Alone for Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Metastasis. Abe, T., Iino, M., Saito, S., et al.[2023]

In a study of 126 patients with unresectable stage III non-small-cell lung cancer, 56% were eligible for durvalumab after chemoradiotherapy, and those who were ineligible had significantly shorter progression-free survival (9.7 months vs. 18.4 months) and overall survival (26.4 months vs. 58.7 months).

The research indicates that durvalumab is safe and beneficial for a considerable number of patients who do not meet the eligibility criteria of the PACIFIC trial, suggesting that its use could be expanded beyond the trial's limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study. Boys, E., Gao, B., Hui, R., et al.[2023]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. [2023]

3. Ireland pubmed.ncbi.nlm.nih.gov

Anti PD-L1 DUrvalumab combined with Cetuximab and RadiOtherapy in locally advanced squamous cell carcinoma of the head and neck: A phase I/II study (DUCRO). [2023]

4. 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]

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

Association of Driver Oncogene Variations With Outcomes in Patients With Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Consolidative Durvalumab. [2023]

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

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. [2023]

7. 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]

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

Rationale and Design of a Single-Arm, Phase 2, Multi-Center Study of Chemo-Immunotherapy Followed by Hypo-Fractionated RT and Maintenance Immunotherapy in Patients With Unresectable Stage III NSCLC: The DEDALUS Trial. [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

Comparison of the Efficacy and Toxicity of Concurrent Chemoradiotherapy and Durvalumab and Concurrent Chemoradiotherapy Alone for Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Metastasis. [2023]

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

Comparison of 2-Weekly Versus 4-Weekly Durvalumab Consolidation for Locally Advanced NSCLC Treated With Chemoradiotherapy: A Brief Report. [2022]

11. Singapore pubmed.ncbi.nlm.nih.gov

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study. [2023]