Phase II Trial of Pembrolizumab in Recurrent or Metastatic HNSCC

Study Overview
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Brief Summary
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A single-arm phase II trial to assess the efficacy and safety profile of pembrolizumab in patients with performance status of 2 with recurrent or metastatic squamous cell carcinoma of the head and neck. Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months

Official Title
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A Phase II Trial to Assess the Efficacy and Safety Profile of Pembrolizumab in Patients With Performance Status 2 With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies. Measurable disease evaluated by RECIST v1.1 WHO performance status of 2 Life expectancy of at least 12 weeks Aged ≥ 18 years of age Adequate Bone marrow function: Absolute neutrophils grade 0 or 1 (using CTCAE v5) Platelets grade 0 or 1 Haemoglobin grade 0 or 1 Adequate renal function: Creatinine grade 0 or 1 Calculated glomerular filtration rate (GFR) ≥ 50 mL/min estimated using validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula). If calculated GFR is < 50 mL/min then an isotope GFR assessment (Cr51-EDTA or 99mTc-DTPA) should be performed. If an isotope GFR test is unavailable an estimation from 24 hour urine collection may be used Adequate liver function: Serum bilirubin grade 0 or 1 AST and ALT grade 0 or 1 (up to grade 2 for patients with liver metastases) Willing to use contraception for the duration of trial treatment and for 120 days after completion of treatment Willing to have a new biopsy, if site of disease is accessible and considered safe to biopsy by investigator If newly obtained samples cannot be obtained (e.g. inaccessible disease or patient safety concern) sites may submit archival tissue only upon agreement from the sponsor Able to give informed consent, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options Willing and able to comply with the protocol for the duration of the study, including the treatment plan, investigations required and follow up visits Exclusion Criteria: Patients with undifferentiated nasopharyngeal or sino-nasal cancers Disease suitable for treatment with curative intent Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent Any investigational agents within 4 weeks prior to registration Anti-cancer monoclonal antibody therapy within 4 weeks prior to registration Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to registration Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment Grade 3 or 4 peripheral neuropathy Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician's judgment, could interfere with patient safety or obtaining informed consent Active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they: Are stable, without evidence of progression for at least four weeks prior to the first dose of trial treatment Have no evidence of new or enlarging brain metastases Have no evidence of leptomeningeal disease Are not using steroids for at least 7 days prior to trial treatment Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected) NB: Without known history, testing is required to determine eligibility. Hepatitis C antibody testing is allowed for screening purposes in sites where HCV RNA is not part of standard of care Immunocompromised patients (e.g. known HIV positive status)* Prior organ transplantation including allogenic stem-cell transplantation Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids, or current pneumonitis/interstitial lung disease Active infection requiring systemic therapy Has received a live vaccine within 30 days prior to registration (seasonal flu vaccines that do not contain live virus are permitted) 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 trial treatment (NB: the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC) Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with the following are eligible: Autoimmune-related hyperthyroidism or autoimmune-related hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone Vitiligo Psoriasis Current use of immunosuppressive medication, except for the following: intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisolone or equivalent (after approval by UCL CTC) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) *Testing for HIV for the POPPY trial is not mandatory, however if this test has been done the result should be known prior to registration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pembrolizumab + best supportive care<br>Best supportive care and pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months | Drug: Pembrolizumab<br>* Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate at 24 weeks assessed using iRECIST | Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST | 24 weeks after registration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate assessed using iRECIST | Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST | 12 months after registration | 
| Best Response Rate- measured using the change from baseline tumour size. Assessed using iRECIST. | Best Response Rate, defined as proportion of patients who have a CR or PR as their best response, measured using the change from baseline tumour size, assessed using iRECIST | 6 months after registration | 
| Clinical Benefit Rate -defined as patient's best response rate lasting at least 18 weeks | Clinical Benefit Rate, defined as proportion patients who have achieved CR, PR or SD as their best response lasting at least 18 weeks | From start of treatment to 30 months post start of treatment | 
| Duration of Response- defined as the time from first documented evidence of CR or PR until disease progression or death. | Duration of Response, defined as the time from first documented evidence of CR or PR until disease progression or death | From start of treatment to 30 months post start of treatment | 
| Time to Progression -defined as time from registration to the first documented disease progression | Time to Progression, defined as time from registration to the first documented disease progression | From registration to 30 months post start of treatment | 
| Progression Free Survival defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first. | Progression Free Survival, defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first. | From registration to 30 months post start of treatment | 
| Overall Survival- defined as the time from registration to death due to any cause. | Overall Survival, defined as the time from registration to death due to any cause. | From registration to 30 months post start of treatment | 
| Frequency and severity of adverse events- throughout the patient's treatment and until 6 months after completion of trial treatment. | Frequency and severity of adverse events | From date of registration until 6 months after completion of trial treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer, Metastatic Head and Neck Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Pembrolizumab