Combining immune therapy with chemoradiation for advanced head and neck cancer

Phase II Non-Randomised Controlled Trial Of Concomitant Immune Check Point Inhibitor With Radiotherapy And Chemotherapy Or Cetuximab In Advanced Non Metastatic Head And Neck Cancer

This study is testing if adding a new immune therapy to standard treatment can help people with advanced head and neck cancer feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 16 Years and up
• Sex: All
• Sponsor: Kuwait Cancer Control Center (Academic / other)
• Drugs / interventions: Pembrolizumab, cetuximab, chemotherapy, immunotherapy, radiation, ipilimumab, avelumab, nivolumab
• Locations: 1 site (Kuwait)
• Trial ID: NCT03532737 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the safety and efficacy of pembrolizumab, a PD-1 inhibitor, when used alongside standard chemoradiation for patients with locally advanced non-nasopharyngeal head and neck cancer. The study aims to assess the tolerability and toxicity of this combination treatment, as well as evaluate response rates and progression-free survival. The trial is particularly relevant given the challenges of systemic failure in head and neck cancer despite initial treatment success. Participants will receive treatment at the Kuwait Cancer Control Center.

Who should consider this trial

Good fit: Ideal candidates include patients with stage III or IVA squamous cell carcinoma of the oropharynx, hypopharynx, oral cavity, or larynx who are medically fit for chemoradiation.

Not a fit: Patients with non-squamous cell carcinomas or those with earlier stage disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes and survival rates for patients with advanced head and neck cancer.

How similar studies have performed: Other studies have shown promising results with PD-1 inhibitors in metastatic head and neck cancer, suggesting potential for success in this novel combination approach.

Eligibility criteria

Inclusion Criteria:

* The patient has pathologically proven squamous cell carcinoma arising in the oropharynx, hypopharynx, oral cavity, or larynx
* The patient has stage III or IVA disease with an expected survival of 12 months.
* The patient is medically suitable to withstand a course of definitive radiation therapy \& chemotherapy.
* Karnofsky performance status is \> 60.
* The patient must have achieved lawful age to provide informed consent according to local or national law .
* Laboratory values performed within 14 days prior to concurrent chemotherapy should be as follows:

  i) Absolute neutrophil count (ANC) ≥ 2000/mm ii) Platelet count ≥ 100.000/mm iii) Hemoglobin ≥ 10g/dl or 100g/L iv) Urea and serum creatinine ≤ 1.5 mg/dl. (for cisplatin) v) Creatinine clearance ≥ 50 ml/min. (for cisplatin) vi) serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) ≤ 2 × upper limit of laboratory normal vii) Serum calcium within normal limits.
* Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy
* Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
* Is eligible for definitive chemoradiation (CRT) and not considered for primary surgery based on investigator decision
* Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
* Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

Exclusion Criteria:

* The patient has evidence of distant metastatic disease.
* The patient has received prior systemic chemotherapy within the last three years.
* The patient has undergone previous surgery for the tumor, other than biopsy.
* The patient has received prior radiation therapy to the H\&N.
* The patient's radiation therapy is considered to be a part of a postoperative regimen following primary surgical resection.
* The patient is pregnant or breast feeding.
* The patient has a medical (e.g. renal impairment) or psychological condition that would not permit the patient to complete the trial or sign informed consent.
* Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with immunotherapy
* Has received a live vaccine within 30 days prior to the first dose of study therapy
* Has not recovered from major surgery prior to starting study therapy
* Has known active Hepatitis B or C
* Has known history of Human Immunodeficiency Virus (HIV)
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
* Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
* Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
* Has had previous allogeneic tissue/solid organ transplant
* Has active infection requiring systemic therapy
* Has a history of severe hypersensitivity reaction to Pembrolizumab, Cisplatin, cetuximab or radiotherapy or their analogs

Where this trial is running

Kuwait

• Kuwait Cancer Control Center — Kuwait, Kuwait (Recruiting)

Study contacts

• Principal investigator: Mustafa S El-Sherify, MD — Kuwait Cancer Control Center
• Study coordinator: Mustafa S El-Sherify, MD

Conditions Locally Advanced Head and Neck Cancer; head and neck cancer; check point inhibitor; Pembrolizumab; Chemoradiation