Evaluation of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases (CABRAMET)
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|ClinicalTrials.gov Identifier: NCT03967522|
Recruitment Status : Recruiting
First Posted : May 30, 2019
Last Update Posted : December 20, 2019
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Renal Cell Carcinoma||Drug: Cabozantinib||Phase 2|
Cabozantinib is a small molecule inhibitor of tyrosine kinases which include MET (hepatocyte growth factor receptor protein), VEGFR (vascular endothelial growth factor receptors), AXL, RET (Rearranged during transfection), FLT3 (Fms-like tyrosine kinase-3), KIT (mast/stem cell factor receptor), ROS1, MER, TYRO3, TRKB (Tropomyosin receptor kinase B) and TIE-2 (angiopoietins receptor). Similar to other TKIs, cabozantinib is a reversible, ATP-competitive inhibitor. Cabozantinib has thus demonstrated significant activity in metastatic clear cell renal cell carcinoma after failure of one or 2 tyrosine kinase inhibitors and is now approved in the second line setting in Europe. Some efficacy was also demonstrated in patients in first line treatment when compared to sunitinib.
Brain metastasis in renal cancer are difficult to treat and cytotoxic systemic therapies are still not used, given by the more or less impermeable blood-brain barrier. The interest of cabozantinib in brain renal cell carcinoma metastases is encouraged by 3 recent cases reports of significant responses of brain metastases including a complete response of brain metastases in one case. Moreover MET receptor surexpression appear more frequent in brain metastases than in other renal cell carcinoma tumor sites. Cabozantinib as multitarget inhibitor including VEGF and MET receptors suggest that it could be a good option. Its efficacy in brain metastases from renal cell carcinoma requires further evaluation.
On this basis, the investigators propose to conduct an open-label exploratory single arm, multicenter prospective phase II trial to assess the efficacy of cabozantinib on brain metastases in metastatic renal cell carcinoma patients.
The relationship between serum markers and efficacy data will be investigated. Serum and plasma sample will be collected at Baseline. MET expression and MET sequencing will be also performed on available tumor tissues.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||77 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CABRAMET: A Phase 2 Study of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases|
|Actual Study Start Date :||November 29, 2019|
|Estimated Primary Completion Date :||September 2022|
|Estimated Study Completion Date :||March 2024|
Experimental: Cabozantinib treatment
All participants will be treated by 60 mg of cabozantinib once daily.
All participants will be treated by 60 mg of cabozantinib once daily. Temporary or permanent discontinuation and/or dose reduction of cabozantinib therapy may be required for the management of some adverse reactions. When dose reduction is necessary, it is recommended to reduce to 40 mg daily, and then to 20 mg daily.
- The non progression rate in brain metastases at 3 months [ Time Frame: At 3 months for each patient ]Tumor assessment in brain will be performed by cerebral MRI at baseline, 1.5 months and 3 months. These cerebral MRI will be reviewed by central review according to the RANO-BM criteria.
- Incidence of adverse events [ Time Frame: Up to 54 months ]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.
- Best response in brain metastases [ Time Frame: Up to follow-up visit month 18 for each patient ]Evaluated according to RANDO-BM criteria.
- Duration of response in brain [ Time Frame: Up to 18 months for each patient ]From the date of inclusion to the date of first documented disease progression.
- Progression-free survival [ Time Frame: Up to 18 months for each patient ]Measured from the date of inclusion to the date of first documented disease progression or death from any cause.
- Overall survival [ Time Frame: Up to 54 months ]Measured from the date of inclusion to the date of death from any cause.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03967522
|Contact: Sylvie NEGRIER, MD, PhD||0478782751 ext +email@example.com|
|Institut de Cancérologie de l'Ouest-Site Paul Papin||Not yet recruiting|
|Angers, France, 49005|
|Contact: Remy DELVA, MD +318.104.22.168.00 firstname.lastname@example.org|
|CHU Besancon||Not yet recruiting|
|Besançon, France, 25030|
|Contact: Fabien CALCAGNO, MD +33381668705 email@example.com|
|Centre Georges François Leclerc||Not yet recruiting|
|Dijon, France, 21079|
|Contact: Sylvain LADOIRE, MD +333 80 73 75 28 firstname.lastname@example.org|
|Centre Leon Berard||Recruiting|
|Lyon, France, 69373|
|Contact: Sylvie NEGRIER, MD, PhD +334 78 78 27 51 email@example.com|
|Centre Val d'Aurelle||Not yet recruiting|
|Montpellier, France, 34928|
|Contact: Diego TOSI, MD +322.214.171.124.04 firstname.lastname@example.org|
|Institut de Cancérologie de la Lorraine||Not yet recruiting|
|Nancy, France, 54519|
|Contact: Lionnel GEOFFROIS, MD +333 83 59 83 31 email@example.com|
|Institut de Cancérologie de l'Ouest-site René Gauducheau||Not yet recruiting|
|Saint-Herblain, France, 44805|
|Contact: Frédéric ROLLAND, MD +3126.96.36.199.76 firstname.lastname@example.org|
|IUCT-Institut Claudius Regaud||Recruiting|
|Toulouse, France, 31059|
|Contact: Christine CHEVREAU, MD +335 31 15 51 51 email@example.com|
|Institut Gustave Roussy||Not yet recruiting|
|Villejuif, France, 94805|
|Contact: Laurence ALBIGES, MD +331 42 11 62 64 firstname.lastname@example.org|
|Principal Investigator:||Sylvie NEGRIER, MD,PhD||Centre Leon Berard|