A study of cabozantinib vs. placebo in subjects with a form of liver cancer who have previously received sorafenib.
- Conditions
- Subjects with Hepatocellular CarcinomaMedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001001-91-BE
- Lead Sponsor
- Exelixis, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 760
1. Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted)
2. The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation)
3. Received prior sorafenib
4. Progression following at least 1 prior systemic treatment for HCC
5. Recovery to = Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically nonsignificant and/or stable on supportive therapy
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 randomization:
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 randomization:
a. serum creatinine = 1.5 x upper limit of normal or calculated creatinine clearance = 40 mL/min (using the Cockroft-Gault equation: (140 – age) x weight (kg)/(serum creatinine × 72 [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 < 1g
10. Child-Pugh Score of A
11. Total bilirubin = 2 mg/dL (= 34.2 µmol/L) within 7 days before randomization
12. Serum albumin = 2.8 g/dL (= 28 g/L) within 7 days before randomization
13. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5.0 upper limit of normal (ULN) within 7 days before randomization
14. Hemoglobin A1c (HbA1c) = 8% within 7 days before randomization (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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 608
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 152
1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
2. Receipt of more than 2 prior systemic therapies for advanced HCC. Additional prior systemic therapies used as adjuvant or local therapy are allowed.
3. Any type of anticancer agent (including investigational) within 2 weeks before randomization
4. Radiation therapy within 4 weeks (2 weeks for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 6 weeks of randomization. Subject is excluded if there are any clinically relevant ongoing complications from prior radiation therapy.
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 duct or common bile duct, or gastric outlet obstruction
ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before randomization,
Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization
5. Prior cabozantinib treatment
6. 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. Eligible subjects must be without corticosteroid treatment at the time of randomization.
7. Concomitant anticoagulation, at therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, low molecular weight heparin (LMWH), thrombin or coagulation factor X (FXa) inhibitors, or antiplatelet agents (eg, clopidogrel). Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (= 1 mg/day), and low-dose LMWH are permitted.
8. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
a. Cardiovascular disorders including
i. Symptomatic congestive heart failure, unstable angina pectoris, or 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 within 6 months before randomization
iv. Thromboembolic event within 3 months before randomization. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible
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 randomization,
Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization
c. Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at leas
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The objective of this study is to evaluate the effect of cabozantinib compared with placebo on overall survival in subjects with advanced HCC previously treated with sorafenib.;Secondary Objective: ;Primary end point(s): Overall survival (OS);Timepoint(s) of evaluation of this end point: The final analysis of OS is event-driven and will be conducted after at least 621 deaths have been observed.<br><br>
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Objective response rate (ORR) per RECIST 1.1<br>Progression-free survival (PFS) per RECIST 1.1;Timepoint(s) of evaluation of this end point: Subjects will be followed until death or the sponsor decides to no longer collect these data.