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

NCT03967522 | Completed Phase 2

• 1 other identifier: CABRAMET (ET19-006)
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 12

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).

Conditions

Metastatic Renal Cell Carcinoma

Keywords

mRCC; cabozantinib; brain metastases

Outcome Measures

Primary Outcomes (1)

• The non progression rate in brain metastases at 6 months

  Tumor assessment in brain will be performed by cerebral MRI at baseline, 1.5 months, 3 months and 6 months. These cerebral MRI will be reviewed by central review according to the RANO-BM criteria.

  At 6 months for each patient

Secondary Outcomes (6)

• Incidence of adverse events

  Up to 54 months

• Best response in brain metastases

  Up to follow-up visit month 18 for each patient

• Duration of response in brain

  Up to 18 months for each patient

• Progression-free survival

  Up to 18 months for each patient

• Overall survival

  Up to 54 months

Study Arms (1)

Cabozantinib treatment

EXPERIMENTAL

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

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

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.

Cabozantinib treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (12)

Institut de Cancérologie de l'Ouest-Site Paul Papin

Angers, 49005, France

Location

CHU Besancon

Besançon, 25030, France

Location

CHU Bordeaux

Bordeaux, 33075, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut de Cancérologie de la Lorraine

Nancy, 54519, France

Location

Hopital Européen Georges Pompidou

Paris, 75015, France

Location

Institut de Cancérologie de l'Ouest-site René Gauducheau

Saint-Herblain, 44805, France

Location

ICANS

Strasbourg, 67000, France

Location

Hopital Foch

Suresnes, 92150, France

Location

IUCT-Institut Claudius Regaud

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Brain Neoplasms

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Sylvie NEGRIER, MD,PhD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: May 30, 2019
• Study Start: November 29, 2019
• Primary Completion: October 22, 2024
• Study Completion: November 1, 2024
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

FR (12)