NCT04454489

Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition

Quad-Shot Radiotherapy in Combination With Immune Checkpoint Inhibition for Advanced/Recurrent Head and Neck Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: Wake Forest University Health Sciences · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.

Detailed description

Primary Objective: Measure the overall response rate for immunotherapy given with quad-shot radiotherapy. Secondary Objective(s) * Measure the response rate at the target lesion. * Measure the response rate at non-target sites in patients with non-target sites. * Evaluate the durability of response at the target lesion. * Evaluate progression-free survival. * Evaluate overall survival. * Assess the tolerability of the combination of quad-shot radiotherapy with immunotherapy in order to assess the feasibility of this treatment regimen. Exploratory Objective: Evaluate the effect of quad- shot administration on increasing the immune activation by treatment with pembrolizumab and investigate possible mechanisms. OUTLINE: Patients receive standard of care pembrolizumab intravenously (IV) over 30 minutes every 3 weeks. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo quad-shot radiation therapy twice daily (BID) on 2 consecutive days between cycles 2-3 or 3-4, 6-7, and 11-12 of pembrolizumab treatment and in the last week of pembrolizumab treatment. After completion of study treatment, patients are followed up at 1 and 2 months for adverse events monitoring. Patients will be followed until death for monitoring survival study endpoints. Frequency of visits will be established by the treating physician and will be done in person or over the phone.

Conditions

• Advanced Head and Neck Squamous Cell Carcinoma
• Recurrent Head and Neck Squamous Cell Carcinoma
• Metastatic Head-and-neck Squamous-cell Carcinoma
• Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck
• Locally Advanced Head and Neck Squamous Cell Carcinoma
• Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck

Interventions

Type	Name	Description
DRUG	Pembrolizumab (immunotherapy)	Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.
RADIATION	Quad-shot palliative radiotherapy	* Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days. * All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3. * Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist. Therefore, the total prescription dose will be: * 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle) * 19.6 Gy in 8 fractions for those that complete 2 cycles * 44.4 Gy in 12 fractions for those that complete 3 cycles

Timeline

• Start date: 2021-02-25
• Primary completion: 2025-02-18
• Completion: 2025-04-30
• First posted: 2020-07-01
• Last updated: 2025-11-19
• Results posted: 2025-11-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study