This phase III trial compares pembrolizumab with radiation therapy to pembrolizumab without radiation therapy (standard therapy) given after pembrolizumab plus chemotherapy for the treatment of patients with squamous cell carcinoma of the head and neck that has spread from where it first started (primary site) to other places in the body (metastatic). Pembrolizumab is a type of immunotherapy that stimulates the body's immune system to fight cancer cells. Pembrolizumab targets and blocks a protein called PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells. Radiation therapy uses high-powered rays to kill cancer cells. Giving radiation with pembrolizumab may be more effective at treating patients with metastatic head and neck cancer than the standard therapy of giving pembrolizumab alone.
PRIMARY OBJECTIVE: I. To compare overall survival (OS) between immunotherapy plus consolidative radiotherapy (CoRT) and immunotherapy alone following non-progression with systemic chemoimmunotherapy. SECONDARY OBJECTIVES: I. To compare progression-free survival (PFS) between the two arms. II. To compare time-to-treatment failure (TTF) between the two arms. III. To determine the risk of non-hematologic high-grade (3 or higher) toxicity with the addition of CoRT. IV. To establish the prognostic value of quantitative positron emission tomography (PET) biomarkers at baseline (standardized uptake value maximum \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\]) for overall survival in both arms. V. To establish the predictive value of (a) structured qualitative read (Hopkins Criteria) and (b) quantitative analysis for assessment of the post-radiotherapy or chemotherapy restaging PET/computed tomography (CT) to evaluate its association with overall survival in both arms. HEALTH-RELATED QUALITY-OF-LIFE (HRQL) OBJECTIVES: I. To compare the time-to-definitive-deterioration (TTDD) between the two arms. (PRIMARY) II. To compare the mean early change in the Functional Assessment of Cancer Therapy - Head \& Neck (FACT-HN) trial outcome index (TOI) between the arms, defined as the difference between the cycle 7 time point and randomization. (SECONDARY) III. To compare the time-to-deterioration (TTD) between the arms (first deterioration). (SECONDARY) IV. To compare the nadir of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) score over the course of study participation between the arms. (EXPLORATORY) V. To compare quality-adjusted survival between the arms. (EXPLORATORY) EXPLORATORY OBJECTIVES: I. To identify differences in patterns-of-failure with respect to local regional and distant recurrences following CoRT versus immunotherapy alone. II. To evaluate the risk of tracheostomy and/or gastrostomy in patients treated with CoRT versus immunotherapy alone. OUTLINE: STEP 1: Patients who have not completed initial systemic therapy prior to enrollment are assigned to Arm T and patients who have completed initial systemic therapy prior to enrollment are assigned to Arm S. ARM T: Patients receive pembrolizumab intravenously (IV) with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV and fluorouracil IV on study. ARM S: Patients proceed directly to Step II. STEP II: Patients are randomized to 1 of 2 arms. ARM A: Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV with radiation therapy on study. Patients also undergo CT, PET/CT, and/or magnetic resonance imaging (MRI) throughout the trial. ARM B: Patients receive one cycle of pembrolizumab IV with carboplatin IV and paclitaxel IV, or with cisplatin IV and fluorouracil IV, or with carboplatin IV, and fluorouracil IV on study and then receive pembrolizumab IV monotherapy on study. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
290
Given IV
Given IV
Undergo CT and/or PET/CT
Given IV
Undergo MRI
Given IV
Given IV
Undergo PET/CT
Ancillary studies
Undergo radiation therapy
Moffitt Cancer Center-International Plaza
Tampa, Florida, United States
RECRUITINGMoffitt Cancer Center - McKinley Campus
Tampa, Florida, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
RECRUITINGEmory University Hospital Midtown
Atlanta, Georgia, United States
Overall survival
Time frame: Time from step 2 randomization to death from any cause, assessed up to 3 years
Progression-free survival
Progression will be evaluated based on international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors guideline.
Time frame: Time from step 2 randomization to disease progression or death, assessed up to 3 years
Time to treatment failure
Time frame: Time from step 2 randomization to the cessation of immunotherapy due to progression, treatment-related toxicity, or death, assessed up to 3 years
Incidence of adverse events (AE)
Patients will be monitored for adverse events using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE). All treatment-emergent and baseline adverse events and hematological/biochemical toxicities based on laboratory measurements, as well as drug related AE's, will be summarized by treatment arm and NCI CTCAE worst grade for step 1 and step 2. Non-hematologic AEs of grade 3 or higher will be assessed by treatment arm.
Time frame: Up to 3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
RECRUITINGSaint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, United States
RECRUITINGSaint Luke's Cancer Institute - Meridian
Meridian, Idaho, United States
RECRUITINGSaint Luke's Cancer Institute - Nampa
Nampa, Idaho, United States
RECRUITINGSaint Luke's Cancer Institute - Twin Falls
Twin Falls, Idaho, United States
RECRUITINGUniversity of Illinois
Chicago, Illinois, United States
RECRUITING...and 41 more locations