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

Launched by ASSOCIATION POUR LA RECHERCHE DES THÉRAPEUTIQUES INNOVANTES EN CANCÉROLOGIE · Aug 23, 2016

Keywords

ClinConnect 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.

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 m...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Histologically confirmed metastatic renal cell carcinoma with a clear cell component.
• • 2. 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).
• • 3. 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).
• • 4. Male or female, age ≥18 years at ICF signature time.
• • 5. Eastern Cooperative Oncology Group (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, cementoplasty or minor surgery; ≥ 4 weeks prior to study entry for major surgery.
• 9. 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.
• • 10. Women of childbearing potential must have a negative serum pregnancy test within 7days prior to treatment initiation.
• • 11. 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.
• • 12. Willingness, for men and women,to use effective contraception during study treatment and for 6 months after last dose of study drug.
• • 13. 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.