Study of Cabozantinib as 2nd Line Treatment in Subjects With Locally Advanced or Metastatic Renal Cell Carcinoma (RCC) With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors

NCT ID: NCT03945773

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 127 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-08
• Study Completion Date: 2030-12-30

Brief Summary

The overall objective of this study is to evaluate the efficacy and safety of cabozantinib as 2nd line treatment in subjects with unresectable, locally advanced or metastatic RCC with a clear-cell component, who progressed after prior Checkpoint Inhibitors (CPI) therapy with ipilimumab and nivolumab in combination or CPI combined with Vascular Endothelial Growth Factor (VEGF)-targeted therapy.

Conditions

Locally Advanced or Metastatic Renal Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

Subjects who radiographically progressed after one prior line by CPI therapy with ipilimumab and nivolumab.

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Oral tablets of 60mg, 40mg and 20 mg.

Cohort B

Subjects who radiographically progressed after one prior line by CPI therapy combined with VEGF-targeted therapy.

Group Type: EXPERIMENTAL

Cabozantinib

Intervention Type: DRUG

Oral tablets of 60mg, 40mg and 20 mg.

Interventions

Cabozantinib

Oral tablets of 60mg, 40mg and 20 mg.

Intervention Type: DRUG

Other Intervention Names

Cabometyx

Eligibility Criteria

Inclusion Criteria

All subjects must fulfil all the following criteria to be included in the study:

1. Subjects must provide a signed informed consent prior to any study-related procedures;

2. Male or female subjects must be aged ≥18 years on the day the informed consent is signed;

3. Subjects must have histologically confirmed unresectable, locally advanced (defined as disease not eligible for curative surgery or radiation therapy) or metastatic RCC with a clear-cell carcinoma component;

4. Subjects must have radiographic disease progression, according to Investigator's judgement following 1st line treatment with CPI (ipilimumab plus nivolumab) (Cohort A) or CPI in combination with VEGF-targeted therapy (Cohort B);

5. Subjects present ≥1 target lesion according to RECIST 1.1 per Investigator;

6. Subjects should have Eastern Cooperative Oncology Group (ECOG) status 0-1;

7. Subjects with treated brain metastases are eligible if metastases have been shown to be stable as per Investigator's judgement;

8. Subjects must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 15 days before baseline:

1. Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).

2. Platelets ≥ 100,000/mm3 (≥ 100 GI/L).

3. Haemoglobin ≥ 9 g/dL (≥ 90 g/L).

4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal (ULN).

5. Total bilirubin ≤ 1.5 × ULN. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 μmol/L).

6. Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation

7. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine or 24-hour urine protein < 1 g.

9. Subject must have recovered to baseline or ≤ Grade 1 per CTCAE v5 from toxicities related to any prior treatments, unless Adverse Events (AE(s)) are clinically nonsignificant and/or stable on supportive therapy as determined by the Investigator;

10. Subject must have completed a steroid taper if he/she had an immune-related adverse event associated with immune CPI;

11. Female subjects of childbearing potential (i.e. less than or equal to 2 years postmenopause and not surgically sterile) must provide a negative pregnancy test within 7 days prior to the start of study treatment. If a urine test cannot be confirmed as negative, a negative serum pregnancy test is required;

12. Female subjects of childbearing potential (i.e. less than or equal to 2 years post-menopause and not surgically sterile) and their partners must agree to use highly effective methods of contraception that alone or in combination result in a failure rate of less than 1% per year when used consistently and correctly during the course of the study and for 4 months after the last dose of study treatment;

13. All male participants must agree to refrain from donating sperm and unprotected sexual intercourse with female partners during the study and for 120 days after the last dose of study treatment;

14. Subjects must be willing and able to comply with study requirements, remain at the investigational site for the required duration of each study visit and be willing to return to the investigational site for the follow up evaluation, as specified in the protocol

15. Subjects must be covered by social security or be the beneficiary of such a system (only applicable for French subjects).

Exclusion Criteria

Subjects will not be included in the study if the subject:

1. Inability to swallow tablets;

2. Was treated with any other investigational medicinal product (IMP) within the last 30 days before baseline;

3. Was previously treated with cabozantinib;

4. Has a contraindication to Magnetic Resonance Imaging (MRI) or contrast medium used for Contrast Tomography (CT)-scan;

5. Presents untreated brain or leptomeningeal metastases, or current clinical or radiographic progression of known brain metastases;

6. Has a diagnosis of a serious cardiovascular disorder:

1. Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, or serious cardiac arrhythmias;

2. Uncontrolled hypertension, defined as sustained blood pressure (BP) (>140 mm Hg systolic or >90 mm Hg diastolic pressure) despite optimal antihypertensive treatment;

3. Stroke (including transient ischaemic attack (TIA)), myocardial infarction (MI) or other ischaemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before screening;

4. History of risk factors for torsades de pointes (e.g., long QT syndrome);

7. Is receiving concomitant anticoagulation with coumarin agents (e.g. warfarin), direct thrombin inhibitor dabigatran, Direct Factor Xa inhibitors betrixaban or platelet inhibitors (e.g. clopidogrel); Note: The following are allowed anticoagulants: prophylactic use of low-dose aspirin for cardioprotection (per local applicable guidelines) and low dose, low molecular weight heparin (LMWH) are permitted. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in patients without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before baseline without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumour.

8. Has a gastrointestinal (GI) disorder including those associated with a high risk of perforation or fistula formation:

(a) Tumours invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction; b) Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before screening; Note: Complete healing of an intra-abdominal abscess must have been confirmed before screening

9. Presents a corrected QT (QTc) interval calculated by the Fridericia formula (QTcF) > 500 msec within 1 month prior to baseline; Note: If a single ECG shows a QTcF with an absolute value > 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility

10. Presents clinically significant haematuria, hematemesis, or haemoptysis of >0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g.

pulmonary haemorrhage) within 3 months before screening;

11. Presents cavitating pulmonary lesion(s) or known endobronchial disease manifestation;

12. Presents lesions invading major pulmonary blood vessels;

13. Has been diagnosed with other clinically significant disorders such as:

1. Serious nonhealing wound/ulcer/bone fracture;

2. Malabsorption syndrome;

3. Uncompensated/symptomatic hypothyroidism;

4. Moderate to severe hepatic impairment (Child-Pugh B or C);

5. Requirement for haemodialysis or peritoneal dialysis;

6. History of solid organ transplantation;

14. Has a predicted life expectancy of less than 3 months;

15. Has had prior surgery within 4 weeks prior to baseline. Note: If the subject has undergone major surgery, complete wound healing must have occurred 1 month prior to baseline

16. Has had palliative radiation therapy for bone within 2 weeks or for radiation fields including viscera within 4 weeks prior to baseline. Note: Resolution/healing of side effects must be complete prior to baseline;

17. Has a history of another active malignancy within 3 years from screening except for locally curable cancers that have been apparently cured, such as low-grade thyroid carcinoma, prostate cancer not requiring treatment (Gleason Grade ≤6), basal or squamous cell skin cancer, superficial bladder cancer, in situ melanoma, in situ prostate, cervix or breast carcinoma or other treated malignancies with <5% chance of relapse according to the Investigator;

18. Has a history of allergy to study treatment components or agents with a similar chemical structure or any excipient used in the formulation as listed in the Summary of Product Characteristics (SmPC) document;

19. Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded;

20. Has a serious medical or psychiatric condition that renders the subject unable to understand the nature, scope and possible consequences of the study, and/or presents an uncooperative attitude;

21. Is pregnant or breastfeeding. A β-human chorionic gonadotrophin (HCG) serum pregnancy test will be performed up to 7 days prior to baseline for all female subjects of childbearing potential (i.e. less than or equal to 2 years post-menopause and not surgically sterile);

22. Is likely to require treatment during the study with drugs that are not permitted by the study protocol;

23. Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the subject's safety

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ipsen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ipsen Medical Director

Role: STUDY_DIRECTOR

Ipsen

Locations

SALK - Salzburger Landesklinik

Salzburg, , Austria

CHRU Besançon

Besançon, , France

Centre Jean Perrin

Clermont-Ferrand, , France

Centre Léon Bérard

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Institut de Cancérologie de Lorraine

Nancy, , France

CHU de Nîmes - Institut de Cancérologie du Gard

Nîmes, , France

Institut Mutualiste Montsouris

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Institut de Cancérologie de l'Ouest

Saint-Herblain, , France

CHU Strasbourg

Strasbourg, , France

Institut Claudius Régaud

Toulouse, , France

Gustave Roussy

Villejuif, , France

Universitätsmedzin Charité

Berlin, , Germany

University Hospital Carl Gustav Carus Dresden

Dresden, , Germany

Universitätsklinikum Essen

Essen, , Germany

University Cancer Center Hamburg Eppendorf

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Klinikum Der Friedrich-Schiller-Universitaet Jena

Jena, , Germany

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Otto-von-Guericke-Universität University hospital Magdeburg

Magdeburg, , Germany

University, Hospital Münster

Münster, , Germany

Caritas Krankenhaus St.Josef Klinik für Urologie

Regensburg, , Germany

University Hospital Tuebingen

Tübingen, , Germany

The Netherlands Cancer Institute - Oncology

Amsterdam, , Netherlands

Maxima Medisch Centrum

Eindhoven, , Netherlands

Leiden University Medical Center

Leiden, , Netherlands

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Hospital de La Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Lucus Augusti

Lugo, , Spain

M.D. Anderson Center Madrid

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Universitätsspital Bern, Inselspital

Bern, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Western General Hospital - Edinburgh Cancer Centre

Edinburgh, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Mount Vernon Hospital

Northwood, , United Kingdom

Royal Cornwall Hospital (RCH) - Sunrise Centre

Truro, , United Kingdom

Countries

Austria; France; Germany; Netherlands; Spain; Switzerland; United Kingdom

References

Albiges L, Schmidinger M, Taguieva-Pioger N, Perol D, Grunwald V, Guemas E. CaboPoint: a phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma. Future Oncol. 2022 Mar;18(8):915-926. doi: 10.2217/fon-2021-1006. Epub 2021 Dec 16.

Reference Type: DERIVED

PMID: 34911359 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.ipsen.com/websites/ipsen_com_v2/wp-content/uploads/2025/01/29153832/F-FR-60000-023-Lay-Results-Summary-1.pdf

Lay language results summary

Other Identifiers

2018-002820-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

F-FR-60000-023

Identifier Type: -

Identifier Source: org_study_id