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

• Status: Unknown status
• Trial end date: 2021-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie
• Treatments: Radium Ra 223 dichloride; Succinylcholine

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.