Renal cell carcinoma patients with bone metastases, with or without visceral metastases.
Conditions
Interventions
Trade Name: XOFIGO
Product Name: XOFIGO
Product Code: BAY 88-8223
Pharmaceutical Form: Injection
Sponsors
A.R.T.I.C. (Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie )
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study have to meet the following criteria: 1.Histologically confirmed metastatic RCC with a clear cell component.. 2.Bone metastases upon bone scan and MRI performed any time within period of 4 weeks prior to study entry, with at least one evaluable unidimensional bone lesion (i.e., =1 malignant tumour mass that can be accurately measured in at least 1 dimension = 10 mm on T1-weighted Magnetic Resonance Imaging [MRI]). Group A: bone metastases (lymph nodes and/or adrenal metastases, and/or = 5 lung metastases of less than 1 cm each, are allowed) . Group B: bone metastases AND visceral metastases upon MRI or CT-scan (according to revised RECIST 1.1 criteria). 3.Naïve patient (first line setting) or patient with disease progression on last therapy (second or third line setting). 4.Male or female, age =18 years at ICF signature time. 5.ECOG performance status of 0 or 1. 6.Good or Intermediate prognostic group according to the International Metastatic Database Consortium (IMDC). 7.At least 4 weeks from the end of a previous systemic treatment, if any, with resolution of all treatment-related toxicity according to NCI CTCAE Version 4.03 grade = 1 except for alopecia. 8.Palliative local treatment allowed if performed = 2 weeks prior to study entry for radiotherapy, cimentoplasty or minor surgery; = 4 weeks prior to study entry for major surgery. 9.Adequate organ function defined by the following criteria: a.Absolute Neutrophils count (ANC) =1 500 cells/mm3 b.Platelets =100 000 cells/mm3 c.Haemoglobin = 9.0 g/dL d.AST and ALT = 2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT =5.0 x ULN e.Total bilirubin = 1.5 x ULN f.Serum creatinine = 1.5 x ULN or calculated creatinine clearance = 50 mL/min g.Urinary protein =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Poor prognostic group according to the IMDC. 2.Prior radiotherapy to = 40% of bone marrow, whole pelvic irradiation and/or prior isotope therapy whatever the isotope (any a- or ß-emitters). 3.Active secondary cancer including prior malignancy from which the subject has been disease-free for = 3 years (however, adequately treated superficial basal cell skin or cervical carcinoma in situ before 4 weeks prior to entry are eligible to the study). 4. Known brain or leptomeningeal involvement. 5. Other concurrent serious illness or medical conditions. 6. Uncontrolled hypertension. 7. Uncontrolled cardiac arrhythmias, angina pectoris, and/or hypertension. History of congestive heart failure, or myocardial infarction within the last 6 months. 8. QTc interval (QTc) assessed by local device > 500ms in the 7 days prior to inclusion. 9. Biphosphonates, denosumab and/or vitamin D supplementation received within 2 weeks before the first injection of XOFIGO®. 10. Active infection requiring systemic antibiotic or anti-fungal medication. 11. Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of the phase I (escalation cohort): is to establish the maximum tolerated dose (MTD) of XOFIGO® in patients with bone metastases only (Group A) or in patients with bone and visceral metastases (Group B). Primary objective of the phase II (expansion cohort): is to establish the most successful doses (MSD) of XOFIGO® based on toxicity and efficacy of XOFIGO® in patients with bone metastases only (Group A) or in patients with bone and visceral metastases (Group B). ;Secondary Objective: Secondary objectives to be evaluated in the Phase I/II (see corresponding endpoints below): •Optimal distribution on Radium-223 scan •Early response upon FNa-PET/TDM •Comparison of FNa-PET scan to whole-body MRI to assess bone response •Bone clinical benefit rate •Overall clinical benefit rate •Pain assessment questionnaire and analgesic consumption •Bone markers •Quality of Life •Time to progression (TTP) •Time to bone progression (TTBP) •Time to occurrence of the first Skeletal-Related Events (SRE) •One-year survival rate (1y-OS) •To evaluate whether new MRI criteria for bone lesions are surrogate markers for bone progression and one-year survival rate ;Primary end point(s): I.Primary endpoint: Phase I (Group A and B): Dose-limiting toxicities (DLT) within the first 6 weeks to determine the MTD. DLT is defined as any XOFIGO® related adverse event occurring between C1D1 and C2D15 and listed below: 1.Haematological toxicity: •Neutrophils 1 related to first administration of XOFIGO® Phase II (Group A and B): Dose-limiting toxicities (DLT) during the phase II DLT period AND efficacy upon MRI +/- FNa-PET to determine the MSD. DLT in phase II: to be determined as in phase I (same definition and causality assessment method). After completion of Phase I, the 45 days,time-window for DLT evaluation (DLT period) may be re-evaluated for phase II based on late-onset toxicities observed in phase I. MSD: to be determined jointly from DLT rate and efficacy r | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): II.Secondary endpoints (to be evaluated at the end of phase II): -Early bone response upon FNa-PET scan -Distribution of radium-223 dichloride into the bone assessed with radium bone scan -Bone response concordance between FNa-PET scan and whole-body MRI -Bone clinical benefit rate (bone objective response or stable disease, BCB) -Overall clinical benefit rate (bone and visceral objective response or stable disease, OCB) -Pain assessment upon Brief Pain Inventory (BPI) and analgesic consumption questionnaire -Changes in bone markers: (Bone formation: bone alkaline phosphatase [bALP], total ALP [tALP], N-terminal type I collagen [PINP]; Bone resorption: C-terminal telopeptide cross-linking of type I collagen [S-CTX-I], cross-linked C-terminal telopeptide of type I collagen [ICTP]), TRACP 5b, sRANKL, osteoprotegerin (OPG) -Time to occurrence of the first Skeletal-Related Events (SRE), SRE including pathological fracture, requirement to initiate radiotherapy, spinal cord compression or requirement for bone surgery -Time to progression (TTP), defined as the time from the first administration of XOFIGO® to the first tumour progression (visceral or bone progression with revised RECIST 1.1 taking into account bone lesions) -Time to bone progression (TTBP) defined as the time from the first administration of XOFIGO® to the bone tumour progression (revised RECIST 1.1 taking into account bone lesions) -1-year overall survival rate (1y-OS) defined as the percentage of patients alive 1 year after 1st administration of XOFIGO® -Quality of life upon FKSI-15 and EQ-5D questionnaires -New MRI criteria as prediction markers for progression and for disease specific and overall survival: •Diffusion weighted imaging (DWI): Apparent diffusion coefficient (ADC) values in the five target bone lesions •Ultra-short echo time (UTE) sequence: T2 measurements in the five target bone lesions •Perfusion weighted imaging (PWI): assessments of the are | — |
Countries
France
Contacts
Public ContactSponsor
A.R.T.I.C. (Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie )
Outcome results
None listed