NCT02880943

Dose-finding, Safety and Efficacy Study of Radium-223 Dichloride (XOFIGO) in RCC Patients With Bone Metastases. (EIFFEL)

Phase I/II Dose-finding, Safety and Efficacy Study of Radium-223 Dichloride (XOFIGO®) in Renal Cell Carcinoma Patients With Bone Metastases.

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, multicentre, open-label, phase I/II study to evaluate the maximum tolerated dose (MTD), and the most successful dose (MSD) of XOFIGO®, in renal cancer patients with metastases to bone, without (Group A) or with (Group B) visceral metastases.

Detailed description

This is a prospective, multicentre, open-label, phase I/II study to evaluate the maximum tolerated dose (MTD), and the most successful dose (MSD) of XOFIGO®, in renal cancer patients with metastases to bone, without (Group A) or with (Group B) visceral metastases. Dose-finding will be performed according to the Continual Reassessment Method (CRM) using either toxicity (escalation cohort) or joined toxicity-efficacy (expansion cohort) endpoints. Two groups of patients will be evaluated: * Group A: patients with bone disease mainly will be treated with XOFIGO® alone. (node and/or adrenal metastases and/or ≤5 lung metastases ≤1cm each are allowed in Group A). * Group B: patients already treated with an ongoing approved Tyrosine Kinase Inhibitor (TKI) for their visceral metastases will be treated with XOFIGO® for bone disease. XOFIGO® will be administered intravenously as a bolus injection every 4 weeks with a maximum of 6 administrations per patient. Four dose levels are available for evaluation : 27.5 kBq/kg, 55 kBq/kg, 88 kBq/kg and 110 kBq/kg. Starting dose for phase I will be 55 kBq/kg. Visit schedule: Selection Patients will come to the hospital at baseline, and screening assessments must be performed within 28 days prior to first XOFIGO® administration. XOFIGO® period Patients will receive an injection of XOFIGO® on Day 1 of each 4 weeks-cycle for a maximum of 6 cycles. Patients will be subject to physical examination, blood sampling and pain evaluation prior to each injection. Scintigraphy of biodistribution of radium-223 dichloride will be realised on C1D1 after the 1st injection of XOFIGO® On C1D15, patients will also come for physical examination and blood sampling. On C2D15 (end of DLT period for phase I), patients will also come for end of DLT period evaluation and will be subject to physical examination and blood sampling. Prior to C3D1 and C5D1, patients will undergo WB-IRM and FNa-PET. End of treatment visit (EOT) will take place 4 weeks after the last administration of XOFIGO®. In the absence of confirmed bone progression at XOFIGO® discontinuation time, patients will continue to undergo WB-IRM and FNa-PET every 2 months until confirmed bone progression or end of follow-up. Confirmation of bone progression upon WB-IRM will be performed 4 weeks after the initial progression is observed. Follow-up Patients will be followed-up for a maximum of 12 months from the 1st administration of XOFIGO®. Number of subjects: Maximum number of patients to be enrolled in the escalation cohort is 21. Maximum number of patients to be enrolled in the expansion cohort is 21. Group A: 2-4 patients; Group B: 38-40 patients.

Conditions

• Clear-cell Metastatic Renal Cell Carcinoma
• Bone Metastases

Interventions

Type	Name	Description
DRUG	XOFIGO	XOFIGO® will be administered intravenously as a bolus injection every 4 weeks with a maximum of 6 administrations per patient. Four dose levels are available for evaluation : 27.5 kBq/kg, 55 kBq/kg, 88 kBq/kg and 110 kBq/kg. Starting dose for phase I will be 55 kBq/kg.

Timeline

• Start date: 2016-10-01
• Primary completion: 2020-10-01
• Completion: 2021-02-01
• First posted: 2016-08-26
• Last updated: 2016-11-08

Locations

5 sites across 1 country: France