Study of cabozantinib in metastatic renal carcinoma in aged fragile patients

Phase 1

• Conditions: Metastatic renal cell carcinoma; MedDRA version: 21.1 Level: LLT Classification code 10050076 Term: Metastatic renal carcinoma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001639-30-ES
• Lead Sponsor: Spanish Oncology Genitourinary Group - SOGUG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-08-09
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 50

Inclusion Criteria

1. Documented histological or cytological diagnosis of renal cell cancer.
2. Measurable disease per RECIST 1.1 as determined by the investigator.
3. Metastatic disease.
4. Patient must have signed the informed consent document.
5. Capable of understanding and complying with the protocol requirements.
6. ECOG-PS 0-2.
7. Patients aged >70 years old with SIOG (Society of Geriatric Oncology) defined fragile population or patients >75 years with or without SIOG defined fragility.
8. No previous treatment for mRCC.
9. Adequate organ function based on standard laboratory tests including haematology, serum chemistry, lipids, coagulation, thyroid function, and urinalysis.
a. Absolute neutrophil count (ANC) = 1500/mm3.
b. Platelets = 100,000/mm3.
c. Hemoglobin = 9 g/dL (= 90 g/L).
d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3.0 × upper limit of normal.
e. Total bilirubin = 1.5 × the upper limit of normal. For subjects with Gilbert’s disease = 3 mg/dL (= 51.3 µmol/L).
f. Fasting serum triglycerides = 2.5 × upper limit of normal AND total cholesterol = 300 mg/dL (= 7.75 mmol/L). Lipid-lowering medication is allowed.
g. HbA1c = 8%. For subjects with a condition (eg, hemoglobin variant) that affects the interpretation of HbA1c results, a fasting glucose = 160 mg/dL (= 8.9 mmol/L).
h. Serum creatinine = 2.0 × upper limit of normal or calculated creatinine clearance = 30 mL/min (= 0.5 mL/sec) using the Cockroft-Gault equation (see section 10.7.5).
i. Urine protein-to-creatinine ratio (UPCR) = 1 mg/mg (= 113.2 mg/mmol) creatinine or 24-hour urine protein < 1 g.
10. 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 course of the study and for 4 months after the last dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1. Previous treatment for mRCC.
2. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before inclusion.
3. Known brain metastases or cranial epidural disease unless adequately treated and stable for at least 3 months before inclusion. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of inclusion.
4. Concomitant anticoagulation at therapeutic doses with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (< 1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted.
5. Chronic treatment with corticosteroids or other immunosuppressive agents (with the exception of inhaled or topical corticosteroids or corticosteroids with a daily dosage equivalent = 10 mg prednisone if given for disorders other than renal cell cancer). Subjects with brain metastases requiring systemic corticosteroid are not eligible.
6. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
a. Cardiovascular disorders:
i. Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
ii. Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
iii. Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before inclusion.
b. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
i. Tumors 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.
ii. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before inclusion. Note: Complete healing of an intra-abdominal abscess must be confirmed before inclusion.
c. Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before inclusion.
d. Cavitating pulmonary lesion(s) or known endobronchial disease manifestation.
e. Lesions invading major pulmonary blood vessels.
f. Other clinically significant disorders such as:
i. Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)- related illness, or chronic hepatitis B or C infection.
ii. Serious non-healing wound/ulcer/bone fracture.
iii. Malabsorption syndrome.
iv. Uncompensated/symptomatic hypothyroidism.
v. Moderate to severe hepatic impairment (Child-Pugh B or C).
vi. Requirement for hemodialysis or peritoneal dialysi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified