Radio-immuno-chemotherapy for Esophageal Cancer

(OPERARADIO Trial)

Overseen By Jennifer Basa

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Manitoba

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Active infection, Organ transplant, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 1

11 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have received anticancer therapy within 15 days before the trial or if you are on certain immunosuppressive medications. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Radio-immuno-chemotherapy for Esophageal Cancer?

Research shows that combining immunotherapy (a treatment that helps the immune system fight cancer) with chemoradiotherapy (a mix of chemotherapy and radiation) can improve survival in patients with esophageal cancer. Studies have found that this combination is safe and may lead to better outcomes compared to using chemoradiotherapy alone. ^{1 2 3 4 5}

Is radio-immuno-chemotherapy safe for esophageal cancer?

Research shows that combining radiotherapy and immune checkpoint inhibitors for esophageal cancer can lead to adverse events (side effects), but these are often not reported as rigorously as the benefits. However, the combination is generally considered safe, with ongoing studies to better understand and manage these side effects. ^{6 7 8 9 10}

How does radio-immuno-chemotherapy differ from other treatments for esophageal cancer?

Radio-immuno-chemotherapy for esophageal cancer is unique because it combines radiotherapy, immunotherapy, and chemotherapy, aiming to enhance the effects of each component. This approach uses a PD-1 inhibitor (a type of immunotherapy) with paclitaxel and platinum-based chemotherapy, and includes both low-dose and conventionally fractionated radiotherapy, which may improve progression-free survival compared to traditional treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

The goal of this study is to assess the safety of delivering concurrent adjuvant chemoradiation or immuno-radiation therapy after EMR/ESD in pT1b/T2N0 esophageal cancer patients. The main objectives of the study are: 1. Assess the feasibility of enrolling 10 patients. 2. Assess the safety of delivering concurrent adjuvant chemoradiation or immunoradiation therapy after EMR/ESD in pT1b/T2 esophageal cancer patients

Research Team

Biniam Kidane

Principal Investigator

University of Manitoba

Eligibility Criteria

This trial is for adults over 18 with early-stage esophageal cancer (T1b/T2N0) who have completed a specific type of surgery (EMR/ESD), can't or won't get their esophagus removed, and meet certain health requirements like body weight and blood counts.

Inclusion Criteria

I have completed a procedure to remove part of the inner layers of my stomach or esophagus.

I am older than 18 years.

Able to provide informed consent

Exclusion Criteria

I have or had an autoimmune or inflammatory disorder.

Participation in another clinical study with an investigational product during the last 4 weeks

History of allogenic organ transplantation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Endoscopic Resection

Participants undergo endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) as a diagnostic and potentially curative procedure

1 week

1 visit (in-person)

Adjuvant Treatment

Participants receive adjuvant immunoradiation therapy or chemoradiation therapy based on eligibility

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Regular visits (in-person and virtual)

Treatment Details

Interventions

• Adjuvant Chemoradiotherapy
• Adjuvant Immunoradiotherapy
• Adjuvant Immunotherapy
• Adjuvant Radiotherapy

Trial Overview The study tests the safety of two additional treatments after surgery: one group gets chemo plus radiation (chemoradiation), while another gets immune therapy plus radiation. The goal is to enroll 10 patients to see if these approaches are safe.

Participant Groups

Group I: Adjuvant chemoradiotherapy Experimental Treatment 1 Intervention

Some patients have medical conditions, i.e., severe auto-immune disease that prohibits them from receiving immunotherapy. In such patients, adjuvant therapy will be provided in the form of concurrent chemoradiotherapy (ARM2).

Group II: Adjuvant Immunoradiotherapy (ARM1) and Adjuvant Immunotherapy (ARM1B) Experimental Treatment 1 Intervention

The primary/preferred adjuvant therapy will be immunoradiotherapy (ARM1); however, if this combination is felt to be too high-risk for specific patients, the next preferred therapy will be immunotherapy without radiation (ARM1B).

Who Is Running the Clinical Trial?

University of Manitoba

Lead Sponsor

Trials

628

Recruited

209,000+

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

Manitoba Medical Service Foundation

Collaborator

Trials

19

Recruited

1,100+

CancerCare Manitoba

Collaborator

Trials

29

Recruited

5,600+

References

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

Ten-year survival with chemotherapy and radiotherapy in patients with squamous cell carcinoma of the esophagus. [2010]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of anti-PD-1 antibody plus chemoradiotherapy in locally advanced esophageal squamous cancer. [2023]

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

Propensity score analysis comparing survival between definitive chemoradiotherapy and esophagectomy with adjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma. [2022]

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

Safety and Feasibility of Radiotherapy Plus Camrelizumab for Locally Advanced Esophageal Squamous Cell Carcinoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant Immunotherapy in Curative Intent Esophageal Cancer Resection Patients: Real-World Experience within an Integrated Health System. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Prognostic parameters for acute esophagus toxicity in intensity modulated radiotherapy and concurrent chemotherapy for locally advanced non-small cell lung cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of immunochemotherapy, immunotherapy, chemotherapy, and targeted therapy as first-line treatment for advanced and metastatic esophageal cancer: a systematic review and network meta-analysis. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity profile of combined immune checkpoint inhibitors and thoracic radiotherapy in esophageal cancer: A meta-analysis and systematic review. [2023]

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

Immune-Related Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Update of latest data for combined therapy for esophageal cancer using radiotherapy and immunotherapy: A focus on efficacy, safety, and biomarkers. [2023]

11. Ireland pubmed.ncbi.nlm.nih.gov

Immunotherapy with or without radiotherapy for metastatic or recurrent esophageal squamous cell carcinoma: A real-world study. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Phase II multicenter trial: first-line immunochemotherapy with or without radiotherapy in metastatic esophageal squamous cell cancer (SCR-ESCC-01). [2023]

13. Japan pubmed.ncbi.nlm.nih.gov

[Multidisciplinary treatment of cancer of the esophagus]. [2013]

14. Netherlands pubmed.ncbi.nlm.nih.gov

The impact of neoadjuvant immunotherapy on perioperative outcomes and survival after esophagectomy for esophageal cancer. [2023]

15. England pubmed.ncbi.nlm.nih.gov

WITHDRAWN. Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus. [2020]