Durvalumab + Radiotherapy for Oral Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug durvalumab (Imfinzi), combined with radiation, can more effectively treat oral cancer while causing fewer side effects. The focus is on squamous cell carcinoma in areas like the mouth and throat. Individuals who have recently undergone surgery to remove the primary tumor and meet specific conditions, such as having certain cancer features that might increase the risk of recurrence, could be suitable candidates. Participants should not have received prior treatments like chemotherapy for the cancer before surgery. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Studies have shown that durvalumab, the drug being tested, is generally well-tolerated by patients with various solid cancers. Research suggests it is safe for use in head and neck cancers. Some patients have experienced side effects, but these are often manageable. Importantly, the FDA has approved durvalumab for treating certain bladder cancers, indicating it has passed strict safety checks for that use.

Intensity Modulated Radiotherapy (IMRT), used with durvalumab in this trial, is a common treatment for oral cancers. While effective, it can cause side effects like mouth sores. In some cases, these sores can be severe and may require feeding tubes. However, IMRT is widely used because it targets cancer cells more precisely.

Both treatments have been studied extensively, and strong evidence supports their safety. However, like all treatments, they can have side effects, which should be discussed with a doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Durvalumab and Intensity Modulated Radiotherapy (IMRT) for oral cancer because it introduces a novel approach to treatment. Unlike traditional chemotherapy or surgery, Durvalumab is an immunotherapy drug, which means it helps your immune system better recognize and attack cancer cells. When paired with IMRT, a precise form of radiation therapy that targets tumors while sparing healthy tissue, this combination has the potential to enhance treatment effectiveness and reduce side effects. This dual approach may offer a more targeted and potentially less toxic option for patients compared to existing treatments.

What evidence suggests that durvalumab combined with radiotherapy could be an effective treatment for oral cancer?

Research has shown that combining durvalumab with radiotherapy yields promising results for treating head and neck cancers. This trial will evaluate the combination of durvalumab with intensity modulated radiotherapy (IMRT) for oral cancer. Some studies suggest that this combination can enhance the body's immune response against cancer cells, potentially leading to better treatment outcomes. Specifically, durvalumab has proven effective in treating lung cancer and shows potential for head and neck cancers. Importantly, it appears to have a favorable safety profile, meaning patients might experience fewer severe side effects compared to drugs like cisplatin. Overall, evidence suggests that durvalumab with radiotherapy could be an effective treatment option for oral cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Siddharth Sheth, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

Citations

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Durvalumab Plus Concurrent Radiotherapy for Treatment ... This single-arm, phase 2 nonrandomized controlled trial assesses the efficacy and safety of durvalumab with concurrent radiotherapy followed by

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03258554

Study Details | NCT03258554 | Radiation Therapy With ... This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer that has spread.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8896055/

Phase Ib study of durvalumab (MEDI4736) in combination with ... The results of the abovementioned study suggest that durvalumab is efficacious in the treatment of lung cancer, and that combining it with CCRT is a promising ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT255209

Safety of radiotherapy with concurrent and adjuvant ... Background: MEDI4736 (durvalumab), a PD-L1 inhibitor, has shown promising antitumor activity and safety in head and neck squamous cell carcinoma (HNSCC).

5. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT03258554

Radiation Therapy With Durvalumab or Cetuximab in ... This phase II/III trial studies how well radiation therapy works with durvalumab or cetuximab in treating patients with head and neck cancer

6. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D4190C00011

A Phase I Study to Evaluate the Safety, Tolerability and ... This is a multicenter, open-label, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics (PK) ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.6065

Safety of radiotherapy with concurrent and adjuvant ... Background: MEDI4736 (durvalumab), a PD-L1 inhibitor, has shown promising antitumor activity and safety in head and neck squamous cell carcinoma ...

8. 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.

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

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...