Dose-finding, Safety and Efficacy Study of Radium-223 Dichloride (XOFIGO) in RCC Patients With Bone Metastases. (EIFFEL) (EIFFEL)
Clear-cell Metastatic Renal Cell Carcinoma, Bone Metastases
About this trial
This is an interventional treatment trial for Clear-cell Metastatic Renal Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed metastatic renal cell carcinoma with a clear cell component.
Bone metastases upon bone scan with no CT 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 (according to revised RECIST 1.1 criteria).
- Patient in a) first (naïve), or b) second or third line setting receiving or about to receive an approved Tyrosine Kinase Inhibitor (patients on mTOR inhibitors are not eligible).
- Male or female, age ≥18 years at ICF signature time.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Good or Intermediate prognostic group according to the International Metastatic Database Consortium (IMDC).
- 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.
- Palliative local treatment allowed if performed ≥ 2 weeks prior to study entry for radiotherapy, cementoplasty or minor surgery; ≥ 4 weeks prior to study entry for major surgery.
Adequate organ function defined by the following criteria:
- Absolute Neutrophils count (ANC) ≥1 500 cells/mm3
- Platelets ≥100 000 cells/mm3
- Haemoglobin ≥ 9.0 g/dL
- 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
- Total bilirubin ≤ 1.5 x ULN
- Estimated glomerular filtration rate upon MDRD ≥ 50 mL/min
- Urinary protein < 2+ by urine dipstick. If dipstick is ≥ 2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is < 2 g per 24 hours
- Corrected calcium ≤ 2.8 mmol/L.
- Women of childbearing potential must have a negative serum pregnancy test within 7days prior to treatment initiation.
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrolment.
- Willingness, for men and women,to use effective contraception during study treatment and for 6 months after last dose of study drug.
- Willingness to comply with protocol requirements.
Exclusion Criteria:
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 α- or β-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. Any other concurrent serious illness or medical conditions including:
- Crohn"s disease or ulcerative colitis
- Bone marrow dysplasia
Known presence of osteonecrosis of the jaw 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. Ongoing biphosphonates, denosumab and/or vitamin D supplementation. 10. Active infection requiring systemic antibiotic or anti-fungal medication. 11. Any contra-indication to MRI, including:
- Carrying a metallic medical device (e.g. pacemaker) or foreign body prohibiting use of MRI
- Known allergy to gadolinium or iodine
- Dysthyroidism precluding usage of iodine contrast agent 12. Pregnant or breast feeding. 13. Participation in another clinical trial with any investigational drug within 30 days prior to study enrolment.
Sites / Locations
- CHU Bordeaux (St. André)
- Centre François Baclesse
- Hôpital Cochin
- Hopital Europeen Georges Pompidou
- Institut Gustave Roussy
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Group A
Group B
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.