Neoadjuvant Immunoradiotherapy in Head & Neck Cancer (NIRT 2-HNC)

Plain English Summary

Neoadjuvant Immunoradiotherapy in Head & Neck Cancer (NIRT 2-HNC) is a Phase 2 clinical trial sponsored by Providence Health & Services studying Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma. This trial tests a combination of immunotherapy (Pembrolizumab) and radiation therapy given before surgery. It is for patients with stage III or IVA HPV-negative head and neck cancer who are scheduled for surgery. Participation involves receiving immunotherapy and radiation for a few weeks before surgery, followed by surgery. Standard treatment options for this type of cancer typically involve surgery, radiation, or chemotherapy, often in combination. The trial aims to enroll 28 participants.

Official Summary

The purpose of this study is to evaluate the efficacy of neoadjuvant immunoradiotherapy (NIRT) prior to surgery for the treatment of stage III and IVA HPV- HNSCC.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients must be at least 18 years old and have a confirmed diagnosis of stage III or IVA HPV-negative head and neck cancer. Patients must be able to undergo surgery and the study treatments. Individuals who have had prior radiation to the head and neck area or have received certain types of immunotherapy or chemotherapy may not be eligible. Participants must have good organ function and an ECOG performance status of 0 or 1. This trial is studying Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see how much of the tumor is destroyed or removed by the treatment before surgery, which could mean a better chance of successful treatment. The specific primary outcome measures are: To determine the pathologic response rate (MPR + pCR) at time of surgery (52 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to improve treatment outcomes for head and neck cancer by using immunotherapy and radiation before surgery, potentially reducing tumor size and making surgery more effective. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This trial explores a novel combination therapy for a specific subset of head and neck cancer, potentially offering a new treatment option and indicating a growing interest in personalized immunothera Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific immunotherapy drug (Pembrolizumab) and radiation plan, including potential side effects. Be prepared for a few weeks of daily treatment before your surgery, which may involve clinic visits for infusions and radiation sessions. Discuss any other medical conditions or medications you are taking with your doctor to ensure you are a suitable candidate. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 28 participants

Interventions

• DRUG: Pembrolizumab — Pembrolizumab is a humanized anti-PD-1 mAb of the IgG4/kappa isotype with a stabilizing S228P sequence alteration in the Fc region.
• RADIATION: Stereotactic Body Radiation Therapy (5 days) — 8Gy x 3 (Mon-Fri) GTV+3mm
• PROCEDURE: Surgical Resection — Surgical Resection of Tumor

Primary Outcomes

• To determine the pathologic response rate (MPR + pCR) at time of surgery (52 weeks)

Secondary Outcomes

• Overall Response Rate (5 years)
• Clinical swallowing evaluation assessed by VFSS (5 years)
• Quality of Life assessed by PSS-HN (5 years)
• Quality of Life assessed by FACT-H&N (5 years)
• Quality of Life assessed by MDASI-HN (5 years)

Full Eligibility Criteria

Inclusion Criteria:

1. Male/female participants who are at least 18 years of age on the day of signing informed consent.
2. Histologically confirmed diagnosis of stage III-IVA HPV-negative HNSCC who are planned for surgical resection and in the opinion of the investigator are able to safely undergo neoadjuvant anti-PD-1 and radiation will be enrolled in this study. Oral cavity, hypopharynx, and larynx cancer are not required to undergo HPV testing by p16 IHC as by convention these tumor locations are assumed to be HPV-negative

   Male participants:
3. A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 75 days, corresponding to time needed to eliminate any study treatment) plus an additional 120 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.

   Female participants:
4. A female participant is eligible to participate if she is not pregnant (see Appendix 3),or breastfeeding and at least one of the following conditions applies:

   1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
   2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 75 days (corresponding to time needed to eliminate any study treatment) plus 30 days (a menstruation cycle) after the last dose of study treatment.
5. The participant must provide (or legally acceptable representative if applicable) written informed consent for the trial.
6. Have provided archival tumor tissue sample collected within the last 6 months or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.

   Note: If submitting unstained slides, slides should be submitted to the testing laboratory within 14 days from the date slides are cut. For archival tissue samples collected \>6 months from screening, PI approval is required.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 10 days prior to the date of enrollment
8. Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment.

Exclusion Criteria:

1. A WOCBP who has a positive serum or urine pregnancy test within 72 hours prior to first dose of pembrolizumab (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
3. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to enrollment

   Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

   Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
4. Has received prior radiotherapy to the head and neck region.
5. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
6. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

   Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) or other solid tumor or hematologic malignancy that have undergone potentially curative therapy outside of the head and neck are not excluded.
9. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging shou

Trial Locations

• University of San Diego, San Diego, California, United States
• Portland Providence Medical Center, Portland, Oregon, United States
• Providence St. Vincent Medical Center, Portland, Oregon, United States

Frequently Asked Questions

Related Conditions

• Head and Neck Cancer
• Head and Neck Squamous Cell Carcinoma
• Oropharyngeal Cancer
• Laryngeal Cancer
• Hypopharyngeal Cancer
• Oral Cavity Cancer
• Nasopharyngeal Cancer
• Thyroid Cancer
• Salivary Gland Cancer
• Esophageal Cancer

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