IRX-2 2015A

• Research type

  Research Study

• Full title

  A Randomized Phase 2 Trial of Neoadjuvant and Adjuvant Therapy with the IRX-2 Regimen in Patients with Newly Diagnosed Stage II, III or IVA Squamous Cell Carcinoma of the Oral Cavity

• IRAS ID

  211178

• Contact name

  James A McCaul

• Contact email

  jmccaul@nhs.net

• Sponsor organisation

  IRX Therapeutics, Inc.

• Eudract number

  2016-000373-21

• Clinicaltrials.gov Identifier

  NCT02609386

• Duration of Study in the UK

  6 years, 6 months, 1 days

• Research summary

  Research Summary

  Squamous cell carcinoma is the most common head and neck cancer with an estimated worldwide incidence in 2000 of more than 551,000, resulting in 217,000 deaths. This type of cancer can affect any part of the oral cavity, including lip, tongue or mouth. Although five-year survival rate is around 50%, patients successfully treated may still have to face consequences of their treatment which could affect appearance, function or quality of life.\nDue to high incidence, inadequacy of currently available therapies and relatively few new therapeutic approaches, treatment of squamous cell carcinoma of the oral cavity is an unmet clinical need. The IRX-2 regimen (study drug) has been studied in two previous studies. These trials established that the IRX-2 regimen has an acceptable safety profile and produced changes in lymphocyte infiltrate in surgically resected tumors when compared to baseline tumor biopsies, suggesting an activation of the immune system against the tumour.\nThe focus of the present clinical trial is to evaluate the effects of the investigational product IRX-2 in patients with Stage II to Stage IVA untreated oral cavity cancer compared to a control arm, where IRX-2 will not be given.\nThe eligible patients for this study will be assigned at random in 2:1 ratio to receive either Regimen 1 (IRX-2 injections with cyclophosphamide, indomethacin, zinc-containing multivitamins and omeprazole) or Regimen 2 (cyclophosphamide, indomethacin, zinc-containing multivitamins, omeprazole without IRX-2 therapy) and treated for 21 days prior to surgery and then postoperatively with a similar but shorter Booster Regimen given every 3 months for 1 year.\nThis clinical trial is being sponsored by IRX Therapeutics. It will take place at 3 sites in the UK and last approximately 6 years 6 months.

  Summary of Results

  GENERAL INFORMATION ABOUT THE STUDY:

  Researchers look at the results of many studies to understand which drugs work and how they work. It takes lots of people in many studies all around the world to advance medical science. This summary only shows the results from this one study.
  The name of this study was a randomized phase 2 trial of neoadjuvant (means before surgery) and adjuvant (means after surgery) therapy with the IRX-2 regimen (the study drug being evaluated) in patients with newly diagnosed stage II, III, or IVA Squamous Cell Carcinoma of the Oral Cavity.

  Protocol number: IRX-2 2015A
  EudraCT number: 2016-000373-21

  This study was sponsored by Eterna Therapeutics (formerly IRX Therapeutics and Brooklyn Immunotherapeutics).
  General information about the clinical study:
  This study took place in the following countries:
  • United States
  • Brazil
  • United Kingdom
  • Canada

  The study started in January 2016 and ended in February 2022.
  The main purpose of this study was to find out the effects, good and/or bad, that the IRX-2 treatments have on patients with squamous cell carcinoma of the oral cavity that is able to be removed by surgery. The study also looked to identify any side effects of the treatments. The blood and tumor samples collected on this study helped assess how the body responds or does not respond to the study drugs and how the study drugs act on the cancer.

  Eligible patients for this study were randomly assigned to one of the two treatment groups: “Regimen 1” or “Regimen 2”. Both treatment groups received the combination of cyclophosphamide, indomethacin, zinc-containing multivitamins, and omeprazole. Patients assigned to “Regimen 1” also received the IRX-2 study drug by injection. In both treatment groups, patients received their assigned treatment over a period of 21 days before their planned surgery . After completing surgery, all patients were to receive post-surgery radiation with or without chemotherapy as determined appropriate by the study doctor. Then, every 3 months for 1 year after surgery, patients were to return to the clinic to receive their assigned treatment regimen over a period of 10 days. After this 1 year period after surgery, patients continued to be followed for 4 years after being enrolled on the study. The reason for this follow up was to compare if patients in one treatment group lived for a longer period of time than the other treatment group without their oral cavity cancer coming back or getting worse.

  A total of 105 patients were enrolled in this study. 67 patients participated in the United States, 35 patients participated in Brazil, 2 patients participated in Canada, and 1 patient participated in the United Kingdom. In total, 70 patients were assigned to the Regimen 1 treatment group and 35 were assigned to the Regimen 2 treatment group. Patients who participated in this trial were aged 23-81 years old.

  WHAT WERE THE RESULTS OF THE STUDY?

  This study showed that the study treatment was well tolerated in both treatment groups. There was a slightly higher percentage of patients who experienced side effects in the Regimen 1 treatment group receiving IRX-2 (95.6%) than in the Regimen 2 treatment group not receiving IRX-2 (88.6%). In both treatment groups, the most frequently reported side effects were related to the gastrointestinal system (e.g., the passage that runs from the mouth to the anus). The most common side effects reported in the Regimen 1 treatment group were nausea and diarrhoea. The most common side effects in the Regimen 2 treatment group were nausea, vomiting, and mouth sores. The next most frequently reported side effects were related to the nervous system, which includes the brain, spinal cord, and the body’s complex network of nerves. Headaches were the most common side effect in both treatment groups. This was reported in a similar percentage of patients in each treatment group (2.9% of patients in Regimen 1 and 5.7% of patients in Regimen 2). Other common side effects reported in the Regimen 1 treatment arm included fatigue (e.g., feeling tired) and injection site pain (e.g., pain where the IRX-2 injections were administered).

  This study showed that patients treated with IRX-2 in the Regimen 1 treatment group did not live a longer period of time without their cancer coming back or getting worse compared to the patients treated without IRX-2 in the Regimen 2 treatment group. The study also did not show that patients treated with IRX-2 in the Regimen 1 treatment group lived longer than patients treated without IRX-2 in the Regimen 2 treatment group. In other words, patients in both groups lived about the same amount of time, no matter what treatment they got.
  The study did show an early trend that patients with more advanced disease (e.g., stage III or IV) may have improved survival outcomes being treated with IRX-2 than patients with less advanced disease (stage I or II). 27.3% of Regimen 1 patients with stage III or IV disease died while 37.5% of Regimen 2 patients with stage III or IV disease died.

  In summary, though this study did not meet its primary objective, it did identify specific patient subgroups that may benefit most from IRX-2. There are no current studies planned to further explore IRX-2, but the results of this study can be used to help drive future research.

  Thank you to all study participants and their caregivers. You can find more details about this study at clinicaltrials.gov.

• REC name

  West of Scotland REC 1

• REC reference

  17/WS/0059

• Date of REC Opinion

  30 May 2017

• REC opinion

  Further Information Favourable Opinion