Phase II Randomized Trial of Radiotherapy with or without Cisplatin for Surgically Resected Squamous Cell Carcinoma of the Head and Neck with TP53 Sequencing

By Robert L. Ferris, MD, PhD

Every year, approximately 40,000 new cases of head and neck squamous cell carcinoma (SCCHN) are diagnosed in the United States. For patients with stage 3-4 locally advanced disease, the current standard of care is surgery followed by postoperative radiotherapy (PORT). Unfortunately, recurrence rates remain high, and for patients with a disruptive p53 genetic mutation, the risk of recurrence is significantly higher. Recent research has shown that adding chemotherapy to PORT improves survival outcomes for some SCCHN patients. More research is needed to determine if patients with the disruptive p53 mutation can also benefit from intensified treatment such as concurrent chemotherapy and PORT.

EA3132 is the first prospective trial to specifically evaluate PORT with or without concurrent chemotherapy (cisplatin) in patients with p53-mutated, surgically resected SCCHN. The study hypothesizes that for SCCHN patients with stage 3-4 locally advanced disease and disruptive p53 mutation, adding cisplatin to PORT will increase disease-free survival by about 20%, from 35% to 55%. With a current enrollment of 130 participants, EA3132 is continuing to accrue towards its goal of 189 participants.

Amendment #8 was recently activated (v.07/24/2024); notable changes include:

• The patient examination within 8 weeks prior to randomization may now be done by the treating medical or radiation oncologist. This eligibility assessment (Section 3.2.2) was previously limited to a head and neck surgeon; the study team hopes that this update will alleviate scheduling difficulties.
• Clarification that protocol treatment must begin within 5 working days after Step 1 (Randomization); previously, it was Step 0 (Pre-Registration) and Step 1 (Randomization)
• Clarification in the Study Parameters table (Section 7) regarding imaging requirements and timing
• The study assay has been updated to FoundationOne CDx^TM
• Clarification that the expected minimum turn-around time for the full FoundationOne CDx^TM assay is 14 days from Foundation Medicine’s receipt of the submitted specimen
• Likewise, Appendix I has been updated to reflect new FoundationOne CDx^TM assay information, including new study-specific forms that must be used to submit EA3132 specimens to Foundation Medicine
  • Sites are reminded that the FoundationOne CDx^TM requisition form packaged with the specimen submission kit should not be used, as it is not study-specific. Doing so may result in the specimen not being appropriately associated with EA3132, and the patient or their insurance may be billed for the testing.

Please note that this is not a complete list of Amendment #8 updates; please review the protocol for all changes. Study resources have been revised to reflect Amendment #8, and are available for download at CTSU.org or on the EA3132 Educational Materials page at ecog-acrin.org.

For any questions regarding the FoundationOne CDx^TM assay or submissions, please contact Foundation Medicine. If you have any questions about the EA3132 study or Amendment #8, please contact the study team.

Learn more about EA3132 at ecog-acrin.org.

Dr. Ferris (University of North Carolina/Lineberger Comprehensive Cancer Center) is the study chair for this trial. The study co-chairs are Christine Chung, MD (Moffitt Cancer Center), and Thomas Galloway, MD (Fox Chase Cancer Center).