Combining Radiation Therapy with Immunotherapy for the Treatment of Metastatic Squamous Cell Carcinoma of the Head and Neck

Summary

Objectives

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 1 of 3 regimen options: Option 1: Pembrolizumab intravenously (IV) on day 1 of each cycle or every other cycle with carboplatin IV on day 1 of each cycle and paclitaxel on day 1 of each cycle or days 1 and 8 of each cycle; Option 2: Pembrolizumab IV on day 1 of each cycle or every other cycle with cisplatin IV on day 1 of each cycle and fluorouracil IV on days 1-4 of each cycle; Option 3: Pembrolizumab IV on day 1 of each cycle or every other cycle with carboplatin IV on day 1 of each cycle and fluorouracil IV on days 1-4 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

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 initial regimen from Arm T. Patients then receive pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 6 weeks for 2 years of total treatment in the absence of disease progression or unacceptable toxicity. Patients also receive radiation therapy once daily (QD) for a total of 30 fractions. In addition, patients undergo CT, PET/CT, and/or magnetic resonance imaging (MRI) throughout the trial.

ARM B: Patients receive one cycle of initial regimen from Arm T. Patients then receive one of the following: 1) Pembrolizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 2 years of total treatment in the absence of disease progression or unacceptable toxicity. 2) Pembrolizumab IV on day 1 of each cycle. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV on day 1 of each cycle. Cycles repeat every 6 weeks for 2 years of total treatment in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, and/or MRI throughout the trial.

After completion of study treatment, participants are followed up for 3 years.