Hepatocellular carcinoma
Conditions
Interventions
Trade Name: COMETRIQ
Product Name: Cabozantinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Cabozantinib
Other descriptive name: Cabozantinib S-malate
Concentration unit: mg milligram(s)
C
Sponsors
Fundació Clinic per a la Recerca Biomèdica
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HCC diagnosed according to American Association for the Study of Liver Diseases (AASLD) guideline. 2. Intolerant to sorafenib according to RESORCE trial definition or patients who received treatment different to sorafenib as first-Line treatment (lenvatinib or atezolizumab bevacizumab). 3. The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation) 4. Recovery to = Grade 1 according to (CTCAE) v.5.0. from toxicities related to any prior treatments, unless the adverse events are clinically non-significant and/or stable on supportive therapy 5. Respect the 15 days of first-line treatment washout before starting cabozantinib 6. Age = 18 years old on the day of consent 7. ECOG performance status of 0 or 1 8. Adequate hematologic function, based upon meeting the following laboratory criteria within 7 days before starting therapy: a. absolute neutrophil count (ANC) = 1200/mm3 (= 1.2 x 109/L) b. platelets = 60,000/mm3 (= 60 x 109/L) c. hemoglobin = 8 g/dL (= 80 g/L) 9. Adequate renal function, based upon meeting the following laboratory criteria within 7 days before starting therapy: a. Serum creatinine = 1.5 × upper limit of normal or calculated creatinine clearance = 40 mL/min (using the Cockroft-Gault equation: (140 – age) x weight (kg)/(serum Creatinine x72 [mg/dL]) for males. (For females multiply by 0.85). AND b. Urine protein/creatinine ratio (UPCR) = 1 mg/mg (= 113.1 mg/mmol) or 24-hour urine protein < 1 g 10. Child-Pugh Score of A 11. Total bilirubin = 2 mg/dL (= 34.2 µmol/L) within 7 days before starting therapy 12. Serum albumin = 2.8 g/dL (=28 g/L) within 7 days before starting therapy 13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5.0 upper limit of normal (ULN) within 7 days before starting therapy 14. Hemoglobin A1c (HbA1c) = 8% within 28 days before starting therapy (if HbA1c results are unavailable [eg, hemoglobin variant], a fasting serum glucose = 160 mg/dL) 15. Antiviral therapy per local standard of care if active hepatitis B (HBV) infection 16. Capable of understanding and complying with the protocol requirements and signed informed consent 17. 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 18. Female subjects of childbearing potential must not be pregnant at screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression, low body weight, or other reasons. 19. Subjects must consent to perform a tumor biopsy within 4 weeks before starting cabozantinib, allowing the acquisition of a tumor sample for performance of correlative studies. A formalin-fixed, paraffin embedded (FFPE) tumor tissue block of tumor sample should be stored at local sites for correlative studies. For these biopsies, subjects must have a soft tissue tumor lesion that can be biopsied at acceptable clinical risk, as judged by the invest
Exclusion criteria
Exclusion criteria: 1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma 2. Radiation therapy (eg, I-131 or Y-90) within 4 weeks (2 weeks for radiation for bone metastases or radionuclide treatment within 6 weeks of starting therapy (subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy) 3. Prior cabozantinib treatment 4. 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 starting therapy. Eligible subjects must be without corticosteroid treatment at the time of starting therapy. 5. Concomitant anticoagulation, at therapeutic doses. Low dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (= 1 mg/day), and low dose LMWH are permitted. 6. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions a. Cardiovascular disorders 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 (eg, Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before starting therapy iii. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to starting therapy c. Major surgery within 2 months before starting therapy. Complete healing from major surgery must have occurred 1 month before starting therapy. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before starting therapy. Subjects with clinically relevant complications from prior surgery are not eligible d. Cavitating pulmonary lesion(s) or endobronchial disease e. Lesion invading a major blood vessel f. including, but not limited to: inferior vena cava, pulmonary artery, or aorta). Subjects with lesions invading the portal vasculature are eligible. g. Clinically significant bleeding risk including the following within 3 months of starting therapy: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, or other signs indicative of pulmonary hemorrhage, or history of other significant bleeding if not due to reversible external factors h. Other clinically significant disorderssuch as: i. Active infection requiring systemic treatment, known infection with human immunodeficiency virus (HIV), or known acquired immunodeficiency syndrome (AIDS)-related illness. Subjects with active hepatitis virus infection controlled with antiviral therapy are eligible. ii. Serious non-healing wound/ulcer/bone fracture iii. Malabsorption syndrome iv. Uncompensated/symptomatic hypothyroidism v. Requirement for hemodialysis or peritoneal dialysis vi. History of solid organ transplantation 7. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding. 8. Moderate or severe ascites 9. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 7 days before starting therapy 10. Inability to swallow tablets 11. Previously identified allergy or hypersensitivity to components of the study treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety profile established by rate of adverse events (AE) with Common Terminology Criteria for Adverse Events (CTCAE)=3 excluding palmar-plantar erythordysthesia, rate of related-AEs and rate of death. The rate of AEs leading to treatment discontinuation.;Secondary Objective: Overall survival (OS), objective response rate (ORR), time to progression (TTP), pattern of progression, post-progression survival (PPS), rate of patients who develop new extra-hepatic spread;Primary end point(s): Rate of AEs with CTCAE=3 excluding palmar-plantar erythordysthesia, Rate of AEs, Rate of related-AEs, Rate of death.;Timepoint(s) of evaluation of this end point: During treatment and 30 days after the last dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Time to progression, Pattern of progression, Overall survival, Post-progression survival, Progression free survival, Rate of patients who develop new extrahepatic spread. ORR;Timepoint(s) of evaluation of this end point: During treatment and follow-up period | — |
Countries
Spain
Contacts
Public ContactClinical Operations department
APICES SOLUCIONES S.L.
Outcome results
None listed