Clinical trial NCT06016699: Immunological Function After Radiation With Either Proton or Photon Therapy
Official title: Effect of Protons Versus Photons on Immunological Function in Head and Neck Cancer: a Pilot Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HNSCC
Head and Neck Cancer
Oropharynx Cancer
Hypopharynx Cancer
Larynx Cancer
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2023-08-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be recruited at the Univeristy Medical Center Groningen (UMCG( and consists of adult patients recently diagnosed with stage III-IV HNSCC. Both photon and proton radiation are standard-of-care treatments for patients with HNSCC.

Brief summary: This is a pilot prospective observational cohort study, comprising patients with head and neck cancer (HNSCC) treated with standard of care definitive (chemo)radiation either with photons or protons. Patients will be assigned for protons or photons based on the guidelines of the National Indication Protocol for Proton therapy of the Netherlands.

Immunological function will be evaluated by the collection of peripheral blood mononuclear cells (PBMCs). Blood samples will be collected at baseline, during (chemo)radiation (end of week 3 and/or before week 4 of treatment) and after completion of (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively 1 week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation). To quantify immunological function, PBMCs collected during (chemo)radiation and after (chemo)radiation will be compared with that before (chemo)radiation (week 0), using IFN-γ-ELISPOT to screen for the presence of antigen-specific T-cell responses. Furthermore, flow cytometry panels will be used to determine global changes in immune cell proficiency.

Histological evaluation will take place at baseline and week 3 to examine changes in immune infiltration within tumour tissue during proton versus photon (chemo)radiation. This biopsy part of the study is optional for the patient. Archival tissue from the biopsy that was taken at diagnosis will be used for the baseline assessments. Biopsy at week 3 week will be taken for all patients who agree to participate in this optional part of the study.


Eligibility criteria: Inclusion Criteria:

* Newly diagnosed stage III-IV HNSCC of the oral cavity, oropharynx, hypopharynx or larynx.
* Treatment with definitive (chemo)radiation (70 Gy with or without weekly cisplatin) with photons or protons.
* Age of 18 years and older.
* Elective or therapeutic bilateral neck irradiation indicated.
* Written informed consent according to local guidelines.

Exclusion Criteria:

* Unilateral radiotherapy of the neck.
* (Diagnostic) resection of the primary tumour.
* Chemoradiation with carboplatin and 5-FU or radiation combined with cetuximab.
* History of an autoimmune disease or other systemic intercurrent disease that might affect the immunocompetence of the patient, or current or prior use (4 weeks before start of the trial) of high dose immunosuppressive therapy.
* Additional malignancy that is progressing or has required active treatment within the past 3 years. Note: participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
* Participation in a study of an investigational agent or has used an investigational device within 4 weeks prior enrolment in this trial. 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.
* Active infection requiring systemic therapy.
* Current pregnancy.
* History or current evidence of any condition, therapy or laboratory abnormality that might confound the results of this trial, interfere with the subject's participation for the full duration of this trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Primary outcomes:
measure: The difference in antigen-specific immunity in HNSCC patients undergoing (chemo)radiation with protons versus photons.
timeFrame: At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)
Secondary outcomes:
measure: Differences in composition and function of circulating immune cells during and after (chemo)radiation with protons versus photons.
timeFrame: At baseline (week 0), during (chemo)radiation (week 3) and after (chemo)radiation (week 9, week 12, week 20, week 34 and week 60, respectively week, 5 weeks, 3 months, 6 months and 12 months after completion of (chemo)radiation)
measure: Immune infiltrate composition within the primary tumour tissue before and during (chemo)radiation with photons versus protons (optional part of the study).
timeFrame: At baseline (week 0) and during (chemo)radiation (week 3)
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen (UMCG)
Study officials:
References: