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


Active: Yes
Cancer Type: Head and Neck Cancer
Skin Cancer (Non-Melanoma)
Unknown Primary
NCT ID: NCT05721755
Trial Phases: Phase III Protocol IDs: EA3211 (primary)
EA3211
NCI-2022-10141
Eligibility: 18 Years and older, Male and Female Study Type: Treatment
Study Sponsor: ECOG-ACRIN Cancer Research Group
NCI Full Details: http://clinicaltrials.gov/show/NCT05721755

Summary

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.

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.

Treatment Sites in Georgia

Emory University Hospital - Midtown
550 Peachtree Street NE
Atlanta, GA 30308
404-686-4411
www.emoryhealthcare.org

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.