caBozantinib in cOllectiNg ductS Renal Cell cArcInoma

Study Overview
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Brief Summary
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This is a single-arm, phase II trial (monocentric) study designed to determine To evaluate activity of Cabozantinib in terms of ORR according to the RECIST 1.1 criteria in Metastatic Collecting Duct Renal Cell Carcinoma

Detailed Description
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This is a single-arm, phase II trial (monocentric)

Official Title
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caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI)

Conditions
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Collecting Duct Carcinoma (Kidney)

Intervention / Treatment
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* Drug: cabozantinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent Form Unresectable, advanced or metastatic collecting ducts carcinoma untreated with any systemic agent for advanced disease Measurable disease as defined by RECIST v1.1 criteria Age ≥18 years ECOG Performance Status 0-1 Any of the following laboratory test findings: Hemoglobin > 9 g/dL (5.6 mmol/L) WBC > 2,000/mm3 Neutrophils > 1,500/mm3 Platelets > 100,000/mm3 AST or ALT < 3 x ULN (< 5 x ULN if liver metastases are present) Total Bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 40 mL/min (measured or calculated by Cockroft-Gault formula) Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis PT-INR/PTT ≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For patients on warfarin, close monitoring of at least weekly evaluations will be performed, until INR is stable based on a measurement at pre-dose, as defined by the local standard of care Availability of a representative FFPE tumor specimen collected within 24 months of starting first-line cabozantinib that enables the definitive diagnosis of CDC (the archival specimen must contain adequate viable tumor tissue to enable candidate biomarkers status; the specimen may consist of a tissue block or at least 15 unstained serial sections; for core needle biopsy specimens, at least two cores should be available for evaluation) Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and for 4 months after the last dose of study treatment Female subjects of childbearing potential must not be pregnant at screening Exclusion Criteria: Previous therapy for advanced disease; any medical adjuvant treatment must have been stopped at least six months before entry into the study History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg]. History of cerebrovascular accidents, including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible Major surgery or trauma within 28 days before to study entry; the such as catheter placement not considered to be major surgery). Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization. Evidence of active bleeding or bleeding diathesis and/or clinically-significant GI bleeding within 6 months before the first dose of study treatment; 3 months for pulmonary hemorrhage and patients with tumor invading or encasing any major blood vessels. Patients with GI disorders associated with a high risk of perforation or fistula formation. Subjects with clinically relevant ongoing complications from prior radiation therapy. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, provision of informed consent, or compliance to study procedures. Previous or ongoing treatment (except for adjuvant therapies) with any of the following anti-cancer therapies: chemotherapy, immunotherapy, target therapies, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Cabozantinib Inability to swallow tablets or capsules.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib<br>All subjects will receive open label Cabozantinib 60 mg orally once daily | Drug: cabozantinib<br>* cabozantinib 60 mg orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | To evaluate activity of Cabozantinib in terms of ORR according to the RECIST 1.1 criteria. | 30 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free Survival (PFS) | To evaluate activity of Cabozantinib in terms of PFS | 30 Month | 
| Overall survival (OS) | To evaluate activity of Cabozantinib in terms of OS | 30 Month | 
| Safety and Tolerability (Adverse Events) | To evaluate tolerability of Cabozantinibv during the treatment in particular the Adverse Events | 30 Month |