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

  • STATUS
    Recruiting
  • End date
    Jan 1, 2023
  • participants needed
    250
  • sponsor
    Ipsen
Updated on 1 August 2021
Investigator
Ipsen Recruitment Enquiries
Primary Contact
Institut Claudius R gaud (0.5 mi away) Contact
+77 other location

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.

Details
Condition Locally Advanced or Metastatic Renal Cell Carcinoma
Treatment Cabozantinib
Clinical Study IdentifierNCT03945773
SponsorIpsen
Last Modified on1 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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 mol/L)
Serum creatinine 2.0 ULN or calculated creatinine clearance 30 mL/min ( 0.5 mL/sec) using the Cockcroft-Gault equation
Urine protein-to-creatinine ratio (UPCR) 1 mg/mg ( 113.2 mg/mmol) creatinine or 24-hour urine protein < 1 g
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
Subject must have completed a steroid taper if he/she had an immune-related adverse event associated with immune CPI
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
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
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
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
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
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
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
History of risk factors for torsades de pointes (e.g., long QT syndrome)
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
\. 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
\. Presents cavitating pulmonary lesion(s) or known endobronchial disease
manifestation
\. Presents lesions invading major pulmonary blood vessels
\. Has been diagnosed with other clinically significant disorders such as
Serious nonhealing wound/ulcer/bone fracture
Malabsorption syndrome
Free thyroxine 4 (FT4) outside the laboratory normal reference range
Uncompensated/symptomatic hypothyroidism
Moderate to severe hepatic impairment (Child-Pugh B or C)
Requirement for haemodialysis or peritoneal dialysis
History of solid organ transplantation
Has a predicted life expectancy of less than 3 months
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
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
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
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
Has rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
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
Is pregnant or breastfeeding. A -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)
Is likely to require treatment during the study with drugs that are not permitted by the study protocol
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
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