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

NCT02880943 | Unknown Phase 1 DMC

• 1 other identifier: EIFFEL
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Clear-cell Metastatic Renal Cell Carcinoma; Bone Metastases

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities (DLT)

  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.

  within 6 weeks after the first injection of XOFIGO

Secondary Outcomes (12)

• Distribution of radium-223 dichloride into the bone assessed with scintigraphy of biodistribution of radium-223 dichloride

  Assessed at day 1 after the first Xofigo injection

• Bone response concordance between FNa-PET scan and whole-body MRI

  up to 12 months

• Bone clinical benefit rate (bone objective response or stable disease, BCB)

  up to 12 months

• Overall clinical benefit rate (bone and visceral objective response or stable disease, OCB)

  up to 12 months

• Changes in bone markers

  up to 12 months

Study Arms (2)

Group A

EXPERIMENTAL

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.

Drug: XOFIGO

Group B

EXPERIMENTAL

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.

Drug: XOFIGO

Interventions

XOFIGO DRUG

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.

Also known as: radium-223

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).
• \. 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).
• \. 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.
• \. 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.

Sponsors & Collaborators

• Association Pour La Recherche des Thérapeutiques Innovantes en Cancérologie: lead

Study Sites (5)

CHU Bordeaux (St. André)

Bordeaux, 33000, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hopital Europeen Georges Pompidou

Paris, 75015, France

Location

Institut Gustave Roussy

Villejuif, 94805 cedex, France

Location

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma

Interventions

radium Ra 223 dichloride; Radium-223

Study Officials

• Stephane OUDARD, MD

  Hôpital Européen Georges Pompidou, Oncology Department

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2016
• First Posted: August 26, 2016
• Study Start: October 1, 2016
• Primary Completion: October 1, 2020
• Study Completion: February 1, 2021
• Last Updated: November 8, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (5)