Concomitant Immune Check Point Inhibitor With Radiochemotherapy in Head And Neck Cancer

• Status: Recruiting
• Trial end date: 2023-10-31
• Target enrollment: 0
• Participant gender: All

Summary

Background: Locally advanced head and neck cancer (HNC) is a challenge as, in spite of initial good control with chemoradiation, the majority of patients fails systemically. In the last 2 years, immune check points inhibitors (mainly Programmed Death (PD)-1 inhibitors) were approved for metastatic/recurrent HNC. The favorable toxicity profile and durable responses was the main benefit of these drugs along the scope of cancers they were approved for.

Aim of the study and methods: This will be a phase II non-randomized trial to define safety and efficacy of combining the PD-1 inhibitor pembrolizumab given concomitantly with the usual standard of care chemoradiation/bioradiation for locally advanced non-nasopharyngeal HNC. Primary end point will be assessment of toxicity and tolerability while the secondary end points will be response rates (RR) and progression free survival (PFS)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kuwait Cancer Control Center
• Treatments: Pembrolizumab

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