Study of cabozantinib in renal cell carcinoma with brain metastases
- Conditions
- Metastatic renal cell carcinoma with non locally pre-treated brain metastases, in first line treatment or after one or two prior treatments.Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000678-41-FR
- Lead Sponsor
- Centre Léon Bérard
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 77
I1. Age = 18 years.
I2. Histologically proven mRCC.
I3. Brain metastases not requiring corticosteroids at dose > 40 mg/day.
I4. At least 1 brain lesion =8 mm in longest diameter or >5 mm if > 1 lesion.
I5. Not previously treated by cabozantinib.
I6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 1.
I7. Life expectancy = 3 months
I8. Adequate organ function as defined by the following criteria.
- Total serum bilirubin 2 x ULN (Gilbert’s disease exempted)
- Serum transaminases and alkaline phosphatases 2.5 x ULN, or in case of liver or bone metastasis 5 x ULN
- Serum creatinine 2 x ULN, creatinine clearance 50 ml/min
- Absolute neutrophil count (ANC) 1 500/mm3
- Platelets 100 000/mm3 (100 G/l)
- Hemoglobin 9.0 g/dl.
I9. Covered by a medical/health insurance.
I10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
...See the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 39
E1. Any local previous treatment of current brain metastases.
E2. Any anti-coagulation therapy (except preventive treatment at low dose).
E3. Contra-indication for MRI (i.e. pace-maker).
E4. Uncontrolled seizures.
E5. Any symptoms of intracranial hypertension.
E6. Any of the following within 12 months prior to treatment initiation: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, ischemic or hemorrhagic stroke including transient ischemic attack.
E7. Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure >90 mmHg, despite optimal medical treatment.
E8. Ongoing cardiac dysrhythmia of grade 2, atrial fibrillation of any grade, QTc interval > 0.43.
E9. Pregnant or breast feeding woman (mandatory negative serum or urinary pregnancy test at study entry for all women of childbearing potential).
E10. Any acute or chronic medical or psychiatric condition or laboratory abnormality that would make the patient unsuited to study participation.
...See the protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the non progression rate in brain metastases at 3 months.;Secondary Objective: • Safety of cabozantinib,especially in terms of neurological tolerance (NCI-CTCAE),<br>• Best response in brain metastases (RANO-BM criteria),<br>• Response rate on the extra-cranial disease at 3 months (RECIST v1.1),<br>• Progression-free survival (PFS), measured from the date of inclusion to the date of first documented disease progression or death from any cause,<br>• Overall survival (OS), measured from the date of inclusion to the date of death from any cause).<br>;Primary end point(s): Non progression rate in brain metastases at 3 months;Timepoint(s) of evaluation of this end point: Tumor assessment in brain will be performed by central review according to the RANO-BM criteria.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Incidence of adverse events (AEs) assessed using the National Cancer Institute – Common Terminology Criteria for Adverse Event (NCI-CTCAE) v5 grading scale, specific registration of neurological event during study duration,<br>• Best response in brain metastases, evaluated according to RANO-BM criteria,<br>• Response on the extracranial disease, evaluated according to RECIST v1.1 criteria,<br>• PFS, measured from the date of inclusion to the date of first documented disease progression or death from any cause. Patients without event will be censored at the time of the last clinical evaluation.<br>• OS, measured from the date of inclusion to the date of death from any cause;<br>;Timepoint(s) of evaluation of this end point: Evaluating according to :<br>• NCI-CTCAE<br>• RANO-BM<br>• RECIST v1.1<br>•date of inclusion to the date of first documented disease progression or death from any cause.