NCT03728179

RACIN in Patients With Advanced TIL-negative Solid Tumors

RACIN, A Phase I Study of the Combination of Nivolumab Associated With Low-dose Radiation, Aspirin/ Celecoxib, and Either Ipilimumab or Low-dose Cyclophosphamide, Followed by Nivolumab Maintenance, in Patients With Advanced, TIL-negative Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: Centre Hospitalier Universitaire Vaudois · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Subjects with locally advanced or metastatic incurable Tumor Infiltrating Lymphocytes (TIL)-negative solid tumors who are not eligible for, declined or failed standard therapy will be treated with a combination nivolumab, low-dose ionizing radiation (RT) (0.5-2 Gy), aspirin (ASA)(cohorts 1 and 2)/celecoxib (cohorts 3, 4 and Phase Ib), and either ipilimumab or low-dose cyclophosphamide. The study comprises 2 phases: The aim of Phase Ia, is to determine safety and tolerability of a given combination therapy, as well as the maximum tolerated dose (MTD) or recommended phase Ib dose (RP1bD) of radiotherapy. Phase Ib aims to further explore safety and tolerability of this treatment in an expansion cohort. In Phase Ia, 4 distinct cohorts will receive the following combination therapy: Cohort1: combination therapy for 5 cycles (C0-C4) which includes: RT 0.5 Gy every 2 weeks (Q2W), Cy (200 mg/m2) Q2W (cycles C0 to C4); ASA (300 mg) daily, with nivolumab 240 mg flat dose Q2W and ipilimumab 1 mg/kg every 6 weeks (Q6W) will be administered (cycles C1 to C4). Cohort2: combination therapy for 5 cycles (C0-C4) which includes: RT 1 Gy every 2 weeks (Q2W), Cy (200 mg/m2) Q2W (cycles C0 to C4); ASA (300 mg) daily, with nivolumab 240 mg flat dose Q2W and ipilimumab 1 mg/kg (Q6W) will be administered (cycles C1 to C4). Cohorts 3a and 4a: Patients will receive Cy (200 mg/m2) Q2W, celecoxib (2x200mg daily), nivolumab (240 mg flat dose) Q2W, and low-dose radiation. Cohort 3a will receive 1 Gy of low-radiation dose and cohort 4a will receive 2 Gy. Cohorts 3b and 4b: Patients will receive nivolumab (240 mg flat dose) Q2W, ipilimumab 1 mg/kg (Q6W), celecoxib (2x200mg daily) and low-dose radiation. Cohort 3b will receive 1 Gy of low-radiation dose and cohort 4b will receive 2 Gy. In Phase Ia, the safety of combination (nivolumab, celecoxib, low-dose irradiation and cyclophosphamide) or (nivolumab, celecoxib, low-dose irradiation and ipilimumab) will be evaluated , and MTD or RP1bD will be defined. RP1bD will be the MTD or, in the absence of dose limiting toxicities (DLTs), the biologically best RT dose based on pharmacodynamics parameters. In Phase Ib, patients will be treated with the MTD or RP1bD dose of RT and will follow the selected schema of treatment used in the Phase Ia cohort 3 or 4. At the end of the 5th cycle, patients eligible for nivolumab maintenance, will be treated with nivolumab at 240 mg Q2W until progression or excessive toxicity; celecoxib will be maintained according to tolerability.

Conditions

• Solid Tumor, Adult

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Low dose irradiation + Nivolumab + Ipilimumab or Cyclophosphamide + Aspirin/Celecoxib	Low Dose Radiation (RT): RT will be administered as single fractions every 2 weeks (Q2W) from cycle C0 to cycle C4. RT will be delivered to a number of metastatic deposits visible by PET/CT, at the PI's discretion. Cyclophosphamide: 200mg/m2 will be administered as intravenous infusion (IV) Q2W from cycle C0 to C4. Nivolumab: 240 mg will be administered as IV Q2W from cycle C1 to C4. Ipilimumab: 1mg/kg will be administered as IV every 6 weeks (Q6W) from cycle C1 to C4 Aspirin: 300mg will be administered orally daily from cycle C1 to C4. All subjects will receive mandatory gastric prophylaxis with an oral H2 antagonist. Celecoxib: 200mg will be administered orally twice a day from cycle C1 to C4. At the end of cycle C4, patients eligible for maintenance will be treated with nivolumab at 240mg Q2W until progression or excessive toxicity; celecoxib will be maintained if the drug is well tolerated

Timeline

• Start date: 2019-01-16
• Primary completion: 2023-10-27
• Completion: 2023-10-27
• First posted: 2018-11-01
• Last updated: 2024-02-20

Locations

1 site across 1 country: Switzerland