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Evaluation of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases (CABRAMET)

Primary Purpose

Metastatic Renal Cell Carcinoma

Status

Recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Cabozantinib

About this trial

This is an interventional treatment trial for Metastatic Renal Cell Carcinoma focused on measuring mRCC, cabozantinib, brain metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Institut de Cancérologie de l'Ouest-Site Paul PapinRecruiting
CHU BesanconRecruiting
CHU BordeauxRecruiting
Centre Jean PerrinRecruiting
Centre Leon BerardRecruiting
Institut de Cancérologie de la LorraineRecruiting
Hopital Européen Georges PompidouRecruiting
Institut de Cancérologie de l'Ouest-site René GauducheauRecruiting
ICANSRecruiting
Hopital FochRecruiting
IUCT-Institut Claudius RegaudRecruiting
Institut Gustave RoussyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cabozantinib treatment

Arm Description

All participants will be treated by 60 mg of cabozantinib once daily.

Outcomes

Primary Outcome Measures

The non progression rate in brain metastases at 3 months

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.

Secondary Outcome Measures

Incidence of adverse events

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

Evaluated according to RANDO-BM criteria.

Duration of response in brain

From the date of inclusion to the date of first documented disease progression.

Progression-free survival

Measured from the date of inclusion to the date of first documented disease progression or death from any cause.

Overall survival

Measured from the date of inclusion to the date of death from any cause.

Full Information

NCT ID

NCT03967522

First Posted

May 27, 2019

Last Updated

August 30, 2023

Sponsor

Centre Leon Berard

1. Study Identification

Unique Protocol Identification Number

NCT03967522

Brief Title

Evaluation of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases

Acronym

CABRAMET

Official Title

CABRAMET: A Phase 2 Study of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 29, 2019 (Actual)

Primary Completion Date

November 2023 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Leon Berard

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a multicenter, open-label, exploratory, single-arm, prospective phase II study to assess the efficacy and safety profile of cabozantinib in patients with brain metastases from metastatic renal cell carcinoma (mRCC).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Renal Cell Carcinoma

Keywords

mRCC, cabozantinib, brain metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

77 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cabozantinib treatment

Arm Type

Experimental

Arm Description

All participants will be treated by 60 mg of cabozantinib once daily.

Intervention Type

Drug

Intervention Name(s)

Cabozantinib

Intervention Description

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.

Primary Outcome Measure Information:

Title

The non progression rate in brain metastases at 3 months

Description

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.

Time Frame

At 3 months for each patient

Secondary Outcome Measure Information:

Title

Incidence of adverse events

Description

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.

Time Frame

Up to 54 months

Title

Best response in brain metastases

Description

Evaluated according to RANDO-BM criteria.

Time Frame

Up to follow-up visit month 18 for each patient

Title

Duration of response in brain

Description

From the date of inclusion to the date of first documented disease progression.

Time Frame

Up to 18 months for each patient

Title

Progression-free survival

Description

Measured from the date of inclusion to the date of first documented disease progression or death from any cause.

Time Frame

Up to 18 months for each patient

Title

Overall survival

Description

Measured from the date of inclusion to the date of death from any cause.

Time Frame

Up to 54 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Sylvie NEGRIER, MD, PhD

Phone

0478782751

Ext

+33

sylvie.negrier@lyon.unicancer.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sylvie NEGRIER, MD,PhD

Organizational Affiliation

Centre Leon Berard

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institut de Cancérologie de l'Ouest-Site Paul Papin

City

Angers

ZIP/Postal Code

49005

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Remy DELVA, MD

Phone

+332.41.35.27.00

remy.delva@ico.unicancer.fr

Facility Name

CHU Besancon

City

Besançon

ZIP/Postal Code

25030

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fabien CALCAGNO, MD

Phone

+33381668705

f.calcagno@chu-besancon.fr

Facility Name

CHU Bordeaux

City

Bordeaux

ZIP/Postal Code

33075

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alain RAVAUD, MD

alain.ravaud@chu-bordeaux.fr

Facility Name

Centre Jean Perrin

City

Clermont-Ferrand

ZIP/Postal Code

63011

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hakim MAHAMMEDI, MD

hakim.mahammedi@clermont.unicancer.fr

Facility Name

Centre Leon Berard

City

Lyon

ZIP/Postal Code

69373

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Sylvie NEGRIER, MD, PhD

Phone

+334 78 78 27 51

sylvie.negrier@lyon.unicancer.fr

Facility Name

Institut de Cancérologie de la Lorraine

City

Nancy

ZIP/Postal Code

54519

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lionnel GEOFFROIS, MD

Phone

+333 83 59 83 31

l.geoffrois@nancy.unicancer.fr

Facility Name

Hopital Européen Georges Pompidou

City

Paris

ZIP/Postal Code

75015

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Stéphane OUDARD, MD

stephane.oudard@aphp.fr

Facility Name

Institut de Cancérologie de l'Ouest-site René Gauducheau

City

Saint-Herblain

ZIP/Postal Code

44805

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Frédéric ROLLAND, MD

Phone

+332.40.67.99.76

frederic.rolland@ico.unicancer.fr

Facility Name

ICANS

City

Strasbourg

ZIP/Postal Code

67000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Philippe BARTHELEMY, MD

p.barthelemy@icans.eu

Facility Name

Hopital Foch

City

Suresnes

ZIP/Postal Code

92150

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Raffaele RATTA, MD

r.ratta@hopital-foch.com

Facility Name

IUCT-Institut Claudius Regaud

City

Toulouse

ZIP/Postal Code

31059

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Loic MOUREY, MD

Phone

+335 31 15 51 51

mourey.loic@iuct-oncopole.fr

Facility Name

Institut Gustave Roussy

City

Villejuif

ZIP/Postal Code

94805

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Laurence ALBIGES, MD

Phone

+331 42 11 62 64

laurence.albiges@gustaveroussy.fr

12. IPD Sharing Statement

Learn more about this trial

Evaluation of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC) With Brain Metastases

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