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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

  • Clinicaltrials.gov identifier

    NCT03945773

  • Recruitment Status

    Recruiting

  • First Posted

    May 10, 2019

  • Last update posted

    May 27, 2021

Study Description

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.

  • Condition or Disease:Locally Advanced or Metastatic Renal Cell Carcinoma
  • Intervention/Treatment: Drug: Cabozantinib
  • Phase: Phase 2

Detailed Description

N/A

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 250 participants
  • Allocation: Non-Randomized
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase II, Multicentre, Open-label Study of Cabozantinib as 2nd Line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic Renal Cell Carcinoma With a Clear-Cell Component Who Progressed After 1st Line Treatment With Checkpoint Inhibitors.
  • Actual Study Start Date: January 2020
  • Estimated Primary Completion Date: February 2022
  • Estimated Study Completion Date: January 2023

Arms and interventions

Arm Intervention/treatment
Experimental: Cohort A
Subjects who radiographically progressed after one prior line by CPI therapy with ipilimumab and nivolumab.
Drug: Cabozantinib
Oral tablets of 60mg, 40mg and 20 mg.
Experimental: Cohort B
Subjects who radiographically progressed after one prior line by CPI therapy combined with VEGF-targeted therapy.
Drug: Cabozantinib
Oral tablets of 60mg, 40mg and 20 mg.

Outcome Measures

  • Primary Outcome Measures: 1. Objective response rate (ORR) [ Time Frame: up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by Independent Central review
  • Secondary Outcome Measures: 1. Objective response rate (ORR) [ Time Frame: up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator
  • 2. Time to response (TTR) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 3. Duration of response (DOR) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 4. Disease control rate (DCR) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 5. Progression-free survival (PFS) [ Time Frame: Every 12 weeks up to 42 months ]
    Assesses by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 assessed by the Investigator and Independent Central review
  • 6. Change in disease-related symptoms [ Time Frame: Every 12 weeks up to 42 months ]
    Assessed by the Functional Assessment of Cancer Therapy-Kidney Cancer Symptom Index (FKSI-DRS) questionnaire.
  • 7. Overall survival (OS) [ Time Frame: Every 12 weeks starting after End of Study Treatment visit (30 days after the last dose) until the subject expires or the end of the study (18 months after the last subject received the first cabozantinib dose), whichever occurs first. ]

Eligibility Criteria

  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

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 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. Free thyroxine 4 (FT4) outside the laboratory normal reference range;

4. Uncompensated/symptomatic hypothyroidism;

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

6. Requirement for haemodialysis or peritoneal dialysis;

7. 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

Contacts and Locations

Contacts

Contact: Ipsen Recruitment Enquiries see email clinical.trials@ipsen.com

Locations

Austria
SALK - Salzburger Landesklinik
Salzburg

Austria
Medical University of Vienna AKH
Vienna

France
CHRU Besançon
Besançon

France
CHU Bordeaux Saint André
Bordeaux

France
Centre Jean Perrin
Clermont-Ferrand

France
Centre Hospitalier
La Roche-sur-Yon

France
Hôpital privé Le Bois
Lille

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
Hôpital Georges Pompidou
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
CHU Bretonneau
Tours

France
Gustave Roussy
Villejuif

Germany
Universitätsmedzin Charité
Berlin

Germany
University Hospital Carl Gustav Carus Dresden
Dresden

Germany
University Clinic Erlanger
Erlangen

Germany
Universitätsklinikum Essen
Essen

Germany
Klinikum der J.W. Goethe
Frankfurt

Germany
University Cancer Center Hamburg Eppendorf
Hamburg

Germany
Medizinische Hochschule Hannover
Hannover

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

Netherlands
The Netherlands Cancer Institute - Oncology
Amsterdam

Netherlands
Maxima Medisch Centrum
Eindhoven

Netherlands
Leiden University Medical Center
Leiden

Netherlands
Universitair Medisch Centrum Utrecht
Utrecht

Spain
Hospital Universitario Vall d'Hebrón
Barcelona

Spain
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
Clínica Universidad de Navarra
Pamplona

Spain
Hospital Madrid Norte Sanchinarro
Sanchinarro

Spain
Hospital Universitario Marqués de Valdecilla
Santander

Switzerland
Universitätsspital Bern, Inselspital
Bern

Switzerland
Centre Hospitalier Universitaire Vaudois
Lausanne

Switzerland
Kantonsspital St. Gallen
Saint Gallen

United Kingdom
Western General Hospital - Edinburgh Cancer Centre
Edinburgh

United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow

United Kingdom
Royal Free Hospital London NHS Trust
London

United Kingdom
The Christie NHS Foundation Trust
Manchester

United Kingdom
Mount Vernon Hospital
Northwood

United Kingdom
Royal Cornwall Hospital (RCH) - Sunrise Centre
Truro

Sponsors and Collaborators

Ipsen

Investigators

Study Director: Ipsen Medical Director Ipsen

More Information

  • Responsible Party: Ipsen
  • ClinicalTrials.gov Identifier: NCT03945773 History of Changes
  • Other Study ID Numbers: F-FR-60000-023, 2018-002820-18
  • First Posted: May 10, 2019 Key Record Dates
  • Last Update Posted: May 27, 2021
  • Last Verified: May 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: Yes
  • Plan Description: Where patient data can be anonymized, Ipsen will share all individual participant data that underlie the results reported in the published journal article with qualified researchers who provide a valid research question. Study documents, such as the study protocol and clinical study report, are not always available
  • Time Frame: Data are available beginning 6 months and ending 5 years after the publication of the findings in a journal; after this time, only raw data may be available.
  • Access Criteria: Proposals should be submitted to DataSharing@ipsen.com and will be assessed by a scientific review board.
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Product Manufactured in and Exported from the U.S.: Yes
  • Additional relevant MeSH terms: Carcinoma Carcinoma, Renal Cell