NCT05501665

Split Course Adaptive Radiation Therapy With Pembrolizumab With/Without Chemotherapy for Treating Stage IV Lung Cancer

SiCARIO (Split Course Adaptive Radioimmunotherapy) for the Treatment of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Using Biologically-Adaptive Radiotherapy - A Phase I/II Study

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (estimated)
• Sponsor: Vanderbilt-Ingram Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab, cemiplimab, atezolizumab or nivolumab may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs like carboplatin, pemetrexed, and paclitaxel work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.

Detailed description

PRIMARY OBJECTIVES: I. Evaluate the safety of adaptive split course hypo-fractionated radiation therapy (RT) with immunotherapy containing systemic regimens. II. Evaluate efficacy of the use of adaptive split course hypo-fractionated RT with immunotherapy containing systemic regimens. SECONDARY OBJECTIVES: I. Evaluate progression and survival benefit of split course adaptive radioimmunotherapy (SiCARIO) regimen. II. Identify potential functional radiomic biomarkers of response to SiCARIO regimen. III. Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive RT. OUTLINE: PRIMARY OBJECTIVES: I. Evaluate the safety of adaptive split course hypo-fractionated radiation therapy (RT) with immunotherapy containing systemic regimens. II. Evaluate efficacy of the use of adaptive split course hypo-fractionated RT with immunotherapy containing systemic regimens. SECONDARY OBJECTIVES: I. Evaluate progression and survival benefit of split course adaptive radioimmunotherapy (SiCARIO) regimen. II. Identify potential functional radiomic biomarkers of response to SiCARIO regimen. III. Develop real-world clinical and treatment planning workflows for implementation of the Ethos platform for anatomic and biologically adaptive RT. OUTLINE: Patients are assigned to 1 of 11 standard treatment regimens, in combination with radiation therapy, as determined by the tumor histology and PD-L1 status. Patients with non-squamous histology and any PD-L1 status are assigned to arms 1-4. ARM I: Patients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. ARM II: Patients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. ARM III: Patients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. ARM IV: Patients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients with squamous histology and any PD-L1 histology are assigned to arms 5-7 ARM V: Patients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM VI: Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM VII: Patients receive carboplatin, paclitaxel and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients with PD-L1 ≥ 50% are assigned to arms 8-10 ARM VIII: Patients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. ARM IX: Patients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. ARM X: Patients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients with any PD-L1 status or histology who are not a chemotherapy candidate are assigned to arm 11 ARM XI: Patients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial. After completion of study treatment, patients are followed up at 4 weeks, 12 weeks, and then every 12 weeks for 2 years.

Conditions

• Lung Non-Small Cell Carcinoma
• Stage IV Lung Cancer AJCC v8
• Stage III Lung Cancer

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Correlative studies
DRUG	Carboplatin	Given carboplatin
PROCEDURE	Computed Tomography	Undergo PET/CT
OTHER	Fludeoxyglucose F-18	Given IV
DRUG	Nab-paclitaxel	Given nab-paclitaxel
BIOLOGICAL	Pembrolizumab	Given pembrolizumab
DRUG	Pemetrexed	Given pemetrexed
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
RADIATION	Radiation Therapy	Undergo radiation therapy
OTHER	[18-F] (fluoropropyl)-L-glutamate (FSPG) PET scan	Undergo PET scan
BIOLOGICAL	Ipilimumab	Given Ipilimumab
BIOLOGICAL	Nivolumab	Given Nivolumab
BIOLOGICAL	Cemiplimab	Given Cemiplimab
BIOLOGICAL	Atezolizumab	Given Atezolizumab

Timeline

• Start date: 2023-05-09
• Primary completion: 2026-02-01
• Completion: 2027-02-01
• First posted: 2022-08-15
• Last updated: 2024-10-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study