Durvalumab + Radiation Therapy for Pancreatic Cancer

Recruiting at 9 trial locations

Overseen By Eileen M O'Reilly, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: FOLFIRINOX

Must not be taking: Immunosuppressants, PD1 inhibitors

Disqualifiers: Metastatic disease, 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: 10 weeks

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to find out if combining durvalumab with standard stereotactic ablative radiotherapy (SABR) is an effective treatment for people with locally advanced or borderline resectable pancreatic cancer. The researchers will also look at the safety of the combination treatment and any side effects it causes.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not be on other investigational agents or immunosuppressive medications within 28 days before treatment, except with chemotherapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Durvalumab + Radiation Therapy for Pancreatic Cancer?

Research shows that combining durvalumab, an immune therapy drug, with radiation therapy has improved survival in patients with certain types of lung cancer. This suggests that a similar combination might also be beneficial for treating pancreatic cancer. ^{1 2 3 4 5}

Is the combination of Durvalumab and radiation therapy safe for humans?

Durvalumab, also known as Imfinzi or MEDI4736, has been studied for safety in various cancers, including lung cancer. It has been approved for use after chemoradiotherapy in certain lung cancer patients, and safety data from these studies show it is generally well-tolerated, though like all treatments, it can have side effects. ^{1 6 7 8 9}

How is the treatment of Durvalumab combined with radiation therapy unique for pancreatic cancer?

This treatment is unique because it combines Durvalumab, an immune system-boosting drug, with targeted radiation therapy, potentially enhancing the body's ability to fight cancer cells more effectively than traditional treatments alone. ^{2 3 5 10 11}

Research Team

Eileen M O'Reilly, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with pancreatic cancer that's locally advanced or borderline resectable, who've had FOLFIRINOX chemotherapy for 3-6 months without disease progression. They must have good organ function and not be pregnant or breastfeeding. Men and women must agree to contraception, and no recent other cancers or treatments outside the protocol are allowed.

Inclusion Criteria

I have been diagnosed with a type of pancreatic cancer that is locally advanced or borderline resectable.

Hemoglobin ≥ 9 g/dL

AST(SGOT) and ALT(SGPT) ≤ 2.5 X ULN

Exclusion Criteria

I do not have any severe illnesses that could interfere with the study.

Patients who are currently receiving any other investigational agents for therapeutic treatment of their primary cancer.

I may have significant nerve pain or damage, subject to my doctor's approval.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab in combination with stereotactic ablative body radiotherapy (SABR)

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Durvalumab
• Stereotactic Ablative Body Radiotherapy (SABR)

Trial Overview The trial is testing if durvalumab combined with SABR (a type of targeted radiation therapy) is effective in treating pancreatic cancer. Durvalumab is an immunotherapy drug designed to help the immune system attack cancer cells.

Participant Groups

Group I: Durvalumab + SABR Experimental Treatment 2 Interventions

Durvalumab + Stereotactic Ablative Body Radiotherapy

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

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

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 of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., 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]

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 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]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

Durvalumab has been approved for use in patients with locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, based on its efficacy demonstrated in the PACIFIC trial and subsequent analysis of 211 patients in the Expanded Access Program (EAP).

In the EAP, 126 patients who received durvalumab were included, some of whom had oligometastatic disease and a history of autoimmune conditions, indicating that durvalumab may be effective and safe for a broader patient population than previously studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. Faehling, M., Schumann, C., Christopoulos, P., et al.[2020]

Durvalumab, used as a consolidation treatment for locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, demonstrated comparable efficacy in terms of progression-free survival (20.1 months) and overall survival (not reached) to the results of the PACIFIC trial, even in a more advanced patient population.

The study found that durvalumab is safe and effective in real-world settings, with encouraging outcomes for selected stage IV patients and those with autoimmune diseases, suggesting that PD-L1 status should not exclude patients from receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and safety from the German expanded-access program (EAP). Faehling, M., Schumann, C., Christopoulos, P., et al.[2021]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

References

1. 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]

2. China pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. [2020]

8. Ireland pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and safety from the German expanded-access program (EAP). [2021]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Radiotherapy Patterns of Care for Locally-advanced Non-small Cell Lung Cancer in the Pre- and Post-durvalumab Era: A Region-wide Survey in a Japanese Prefecture. [2022]