Randomized phase II study of immune stimulation with Pembrolizumab and radiotherapy in second line therapy of metastatic head and neck squamous cell carcinoma.
This is an open-label, randomized, prospective, multicenter phase II clinical trial of pembrolizumab with or without local radiotherapy in patients with recurrent and/or metastatic HNSCC after progression to platinum-based therapy. All patients will receive pembrolizumab 200mg absolute dose administered every third week. Patients in treatment arm A will receive radiotherapy of one, two or three metastases with a total tumor volume of at least 10cm³ intended to induce tumor cell death acting as an in situ vaccination. Radiotherapy (RT) will be performed conventionally fractioned with single doses of 3Gy to a total dose of 36Gy. There will be a strict time schedule. Radiotherapy will always start on Wednesday. After application of the third radiation dose (Friday) the patients will receive pembrolizumab. After an interruption of radiotherapy for two days (Saturday, Sunday), radiotherapy will be continued. Pembrolizumab will be continued on an every three week schedule until confirmed disease progression according to iRECIST criteria, unacceptable toxicity, patient's wish to stop therapy or a maximal treatment time of 12 months. Tumor assessment will be performed every 9 weeks and will be evaluated according to iRECIST and RECIST. For each patient the same assessment method will be used throughout the study. Toxicity will be assessed according to CTCAE 4.0.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
115
Pembrolizumab (200mg absolute, q3w) combined with radiotherapy (12x3Gy) of one, two or three metastases. Only metastases that perspectively require radiotherapy will be treated. The irradiated tumor volume must be at least 10cm³. Radiotherapy of brain metastases is not allowed.
Pembrolizumab (200mg absolute, q3w)
Bochum, St. Josef-Hospital, Abteilung für Hämatologie und Onkologie
Bochum, Germany
Dresden, Onkologische Gemeinschaftspraxis
Dresden, Germany
Düsseldorf, Universitätsklinikum, Klinik für Strahlentherrapie und Radiologische Onkologie
Düsseldorf, Germany
Erlangen, Universitätsklinikum Strahlenklinik
Best Response According to iRECIST Criteria
Response evaluation will be performed according to iRECIST and RECIST. These iRECIST criteria are the RECIST 1.1 criteria adapted for immunotherapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the small
Time frame: Endpoint is the best response during pembrolizumab treatment (restaging every 9 weeks up to 12 months)
Response Rate According to RECIST
RECIST 1.1 criteria will be used to evaluate response rate
Time frame: restaging every 9 weeks up to 12 months
Assessment of the Duration of Response
The duration of the response will be evaluated in responding patients.
Time frame: restaging every 9 weeks up to 12 months
Assessment of the Progression Free Survival
progression free survival in ITT population Response evaluation will be performed according to iRECIST and RECIST. These iRECIST criteria are the RECIST 1.1 criteria adapted for immunotherapy. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
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Erlangen, Germany
Frankfurt, Universitätsklinikum, Klinik für Strahlentherapie und Onkologie
Frankfurt, Germany
Homburg, Universitätsklinikum, Klinik für Strahlentherapie und Radioonkologie
Homburg, Germany
Regensburg, Universitätsklinikum, Klinik für Strahlentherapie
Regensburg, Germany
Time frame: restaging every 9 weeks up to 12 months
Assessment of the Overall Survival
Overall survival (in months) in ITT population
Time frame: during trial treatment an follow-up, i.e. total of 24 months
Assessment of Toxicity of the Combination of Pembrolizumab and Radiotherapy
Toxicity will be evaluated according to CTCAE 4.0 to assess toxicity of the combination of pembrolizumab and radiotherapy
Time frame: at every pembrolizumab administration (q3w) (up tp 12 months)