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

NCT03945773 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: F-FR-60000-0232018-002820-18
• Study Type: interventional
• Target: 127
• Locations: 7 countries
• Sites: 40

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

Outcome Measures

Primary Outcomes (1)

• Cohort A: Objective Response Rate (ORR) Assessed by Independent Central Review

  ORR was defined as the percentage of participants who achieved a partial response (PR) or complete response (CR) at any timepoint as determined by independent central review per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. The CR was defined as disappearance of all target lesions. The PR was defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. The confidence interval of the ORR was calculated using Clopper-Pearson exact method.

  Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

Secondary Outcomes (8)

• Time to Response (TTR) Assessed by Independent Central Review and Investigator

  Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

• Duration of Response (DOR) Assessed by Independent Central Review and Investigator

  Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

• Disease Control Rate (DCR) Assessed by Independent Central Review and Investigator

  Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

• Progression-free Survival (PFS) Assessed by Independent Central Review and Investigator

  Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

• Cohort B: Objective Response Rate Assessed by Independent Central Review

  Tumour assessments performed at Screening/Baseline (within 28 days prior start of study treatment) and every 12 weeks, up to approximately 40 months

Study Arms (2)

Cohort A

EXPERIMENTAL

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

Drug: Cabozantinib

Cohort B

EXPERIMENTAL

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

Drug: Cabozantinib

Interventions

Cabozantinib DRUG

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

Also known as: Cabometyx

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• All subjects must fulfil all the following criteria to be included in the study:
• Subjects must provide a signed informed consent prior to any study-related procedures;
• Male or female subjects must be aged ≥18 years on the day the informed consent is signed;
• 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;
• 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);
• Subjects present ≥1 target lesion according to RECIST 1.1 per Investigator;
• Subjects should have Eastern Cooperative Oncology Group (ECOG) status 0-1;
• Subjects with treated brain metastases are eligible if metastases have been shown to be stable as per Investigator's judgement;
• Subjects must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 15 days before baseline:
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (≥ 1.5 GI/L).
• Platelets ≥ 100,000/mm3 (≥ 100 GI/L).
• Haemoglobin ≥ 9 g/dL (≥ 90 g/L).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3.0 × upper limit of normal (ULN).
• Total bilirubin ≤ 1.5 × ULN. For subjects with Gilbert's disease ≤ 3 mg/dL (≤ 51.3 μmol/L).
• Serum creatinine ≤ 2.0 × ULN or calculated creatinine clearance ≥ 30 mL/min (≥ 0.5 mL/sec) using the Cockcroft-Gault equation

You may not qualify if:

• Subjects will not be included in the study if the subject:
• Inability to swallow tablets;
• Was treated with any other investigational medicinal product (IMP) within the last 30 days before baseline;
• Was previously treated with cabozantinib;
• Has a contraindication to Magnetic Resonance Imaging (MRI) or contrast medium used for Contrast Tomography (CT)-scan;
• Presents untreated brain or leptomeningeal metastases, or current clinical or radiographic progression of known brain metastases;
• Has a diagnosis of a serious cardiovascular disorder:
• Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, or serious cardiac arrhythmias;
• Uncontrolled hypertension, defined as sustained blood pressure (BP) (\>140 mm Hg systolic or \>90 mm Hg diastolic pressure) despite optimal antihypertensive treatment;
• 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;
• History of risk factors for torsades de pointes (e.g., long QT syndrome);
• 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.
• 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
• 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

Sponsors & Collaborators

• Ipsen: lead

Study Sites (40)

SALK - Salzburger Landesklinik

Salzburg, A-5020, Austria

Location

CHRU Besançon

Besançon, 25000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Institut de Cancérologie de Lorraine

Nancy, 54511, France

Location

CHU de Nîmes - Institut de Cancérologie du Gard

Nîmes, 30029, France

Location

Institut Mutualiste Montsouris

Paris, 75014, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Institut de Cancérologie de l'Ouest

Saint-Herblain, 44800, France

Location

CHU Strasbourg

Strasbourg, 67091, France

Location

Institut Claudius Régaud

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsmedzin Charité

Berlin, D-10117, Germany

Location

University Hospital Carl Gustav Carus Dresden

Dresden, D-1307, Germany

Location

Universitätsklinikum Essen

Essen, D-45147, Germany

Location

University Cancer Center Hamburg Eppendorf

Hamburg, d-20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, D-30625, Germany

Location

Klinikum Der Friedrich-Schiller-Universitaet Jena

Jena, D-07747, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, D-23538, Germany

Location

Otto-von-Guericke-Universität University hospital Magdeburg

Magdeburg, D-39120, Germany

Location

University, Hospital Münster

Münster, D-48149, Germany

Location

Caritas Krankenhaus St.Josef Klinik für Urologie

Regensburg, D-93053, Germany

Location

University Hospital Tuebingen

Tübingen, D-72076, Germany

Location

The Netherlands Cancer Institute - Oncology

Amsterdam, 1066 CX, Netherlands

Location

Maxima Medisch Centrum

Eindhoven, 5604 DB, Netherlands

Location

Leiden University Medical Center

Leiden, 2300-RC, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Lucus Augusti

Lugo, 27003, Spain

Location

M.D. Anderson Center Madrid

Madrid, 28033, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Universitätsspital Bern, Inselspital

Bern, 3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Western General Hospital - Edinburgh Cancer Centre

Edinburgh, EH4 2XU, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Mount Vernon Hospital

Northwood, HA6 2RN, United Kingdom

Location

Royal Cornwall Hospital (RCH) - Sunrise Centre

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34911359 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

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

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 10, 2019
• Study Start: January 8, 2020
• Primary Completion: May 11, 2023
• Study Completion: February 12, 2026
• Last Updated: March 13, 2026
• Results First Posted: December 19, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

ES (4); CH (3); GB (5); NL (4); AU (1); DE (11); FR (12)