- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03967522
Evaluation of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases (CABRAMET)
CABRAMET: A Phase 2 Study of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Ancillary studies:
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
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Sylvie NEGRIER, MD, PhD
- Phone Number: +33 0478782751
- Email: sylvie.negrier@lyon.unicancer.fr
Study Locations
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Angers, France, 49005
- Recruiting
- Institut de Cancérologie de l'Ouest-Site Paul Papin
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Contact:
- Remy DELVA, MD
- Phone Number: +332.41.35.27.00
- Email: remy.delva@ico.unicancer.fr
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Besançon, France, 25030
- Recruiting
- CHU Besançon
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Contact:
- Fabien CALCAGNO, MD
- Phone Number: +33381668705
- Email: f.calcagno@chu-besancon.fr
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Bordeaux, France, 33075
- Recruiting
- CHU Bordeaux
-
Contact:
- Alain RAVAUD, MD
- Email: alain.ravaud@chu-bordeaux.fr
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Clermont-Ferrand, France, 63011
- Recruiting
- Centre Jean Perrin
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Contact:
- Hakim MAHAMMEDI, MD
- Email: hakim.mahammedi@clermont.unicancer.fr
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Lyon, France, 69373
- Recruiting
- Centre LEON BERARD
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Contact:
- Sylvie NEGRIER, MD, PhD
- Phone Number: +334 78 78 27 51
- Email: sylvie.negrier@lyon.unicancer.fr
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Nancy, France, 54519
- Recruiting
- Institut de Cancérologie de la Lorraine
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Contact:
- Lionnel GEOFFROIS, MD
- Phone Number: +333 83 59 83 31
- Email: l.geoffrois@nancy.unicancer.fr
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Paris, France, 75015
- Recruiting
- Hopital Europeen Georges Pompidou
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Contact:
- Stéphane OUDARD, MD
- Email: stephane.oudard@aphp.fr
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Saint-Herblain, France, 44805
- Recruiting
- Institut de Cancérologie de l'Ouest-site René Gauducheau
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Contact:
- Frédéric ROLLAND, MD
- Phone Number: +332.40.67.99.76
- Email: frederic.rolland@ico.unicancer.fr
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Strasbourg, France, 67000
- Recruiting
- ICANS
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Contact:
- Philippe BARTHELEMY, MD
- Email: p.barthelemy@icans.eu
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Suresnes, France, 92150
- Recruiting
- Hôpital FOCH
-
Contact:
- Raffaele RATTA, MD
- Email: r.ratta@hopital-foch.com
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Toulouse, France, 31059
- Recruiting
- IUCT-Institut Claudius Regaud
-
Contact:
- Loic MOUREY, MD
- Phone Number: +335 31 15 51 51
- Email: mourey.loic@iuct-oncopole.fr
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Villejuif, France, 94805
- Recruiting
- Institut Gustave Roussy
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Contact:
- Laurence ALBIGES, MD
- Phone Number: +331 42 11 62 64
- Email: laurence.albiges@gustaveroussy.fr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
I1. Age ≥ 18 years. I2. Histologically proven metastatic Renal Cell Carcinoma. I3. Brain metastases not requiring corticosteroids at dose > 40 mg/day. I4.At least 1 locally untreated brain lesion ≥8mm in longest diameter or >5mm 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 ≤ 5.0 x ULN
- Serum creatinine ≤ 2 x ULN OR 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.
I11. Signed and dated IRB/ICE approved informed consent form. I12. Accepting to use effective contraception (barrier contraceptives) during study treatment and within at least 4 months after final dose of study therapy. Oral contraceptives are not acceptable.
Exclusion Criteria:
E1. Any local previous treatment of current brain metastases. E2. Any anti-coagulation therapy (except preventive treatment at low dose). E3. Contra-indication of Magnetic Resonance Imaging (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.
E11. Any second malignancy within the last 3 years with the exception of basal cell carcinoma, in situ cervical cancer and pT1/a bladder cancer with no evidence of recurrent disease for 12 months.
E12. Patients receiving strong inhibitor or inducer of CYP3A4 especially some anti-epileptic drugs.
E13. Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements.
E14. Participation to another clinical trial that might interfere with the evaluation of the main criterion.
E15. Known hypersensitivity to the active substance or to any of the excipients of cabozantinib.
E16. Patient requiring tutorship or curatorship.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The non progression rate in brain metastases at 3 months
Time Frame: At 3 months for each patient
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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.
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At 3 months for each patient
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 54 months
|
Best response in brain metastases
Time Frame: Up to follow-up visit month 18 for each patient
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Evaluated according to RANDO-BM criteria.
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Up to follow-up visit month 18 for each patient
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Duration of response in brain
Time Frame: Up to 18 months for each patient
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From the date of inclusion to the date of first documented disease progression.
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Up to 18 months for each patient
|
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.
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Up to 18 months for each patient
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Overall survival
Time Frame: Up to 54 months
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Measured from the date of inclusion to the date of death from any cause.
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Up to 54 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sylvie NEGRIER, MD,PhD, Centre LEON BERARD
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Neoplastic Processes
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Carcinoma, Renal Cell
- Carcinoma
- Neoplasm Metastasis
- Brain Neoplasms
Other Study ID Numbers
- CABRAMET (ET19-006)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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