Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
This is a phase 2 single-arm, open-label clinical trial determining efficacy of cabozantinib in combination with ipilimumab/nivolumab and transarterial chemoembolization (TACE) in subjects with hepatocellular carcinoma (HCC). These are subjects who are not candidates for curative intent treatment.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Histologic or radiographic diagnosis of hepatocellular carcinoma
At least one lesion amenable to TACE treatment
Child-Pugh A-B7 (B7 based on Albumin allowed)
Not a candidate for resection or transplantation
Age ≥ 18 years.
Performance status: ECOG performance status ≤2
Must have at least one measurable lesion (either untreated or progressed after previous locoregional treatment)
Adequate organ and marrow function as defined below:
The effects of cabozantinib on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Based on its mechanism of action, ipilimumab can cause fetal harm when administered to a pregnant woman. Females of reproductive potential must use effective contraception during treatment with ipilimumab and for 3 months following the last dose of ipilimumab.
Based on its mechanism of action, nivolumab can cause fetal harm when administered to a pregnant woman. Females of reproductive potential must use effective contraception during treatment with nivolumab and for 5 months following the last dose of nivolumab.
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion criteria
Any type of previous systemic anti-cancer treatment
All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 or baseline
Any locoregional treatment for HCC within 3 months
Vp4 or Vp3 portal vein thrombus
Extrahepatic disease
Patients may not be receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, cabozantinib or other agents used in study.
Concomitant anticoagulation with coumarin agents (eg, warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitors (e.g., rivaroxaban), or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following:
The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 28 days before the first dose of study treatment.
Uncontrolled intercurrent illness including, but not limited to, the following conditions:
ongoing or active infection
symptomatic congestive heart failure
uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment
Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose
unstable angina pectoris
cardiac arrhythmia
evidence of tumor invading GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.
Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose.
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 12 weeks before first dose.
Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation.
Lesions invading any major blood vessels. Subjects with lesions invading the intrahepatic vasculature, including portal vein, hepatic vein, and hepatic artery, are eligible.
Other clinically significant disorders that would preclude safe study participation:
psychiatric illness/social situations that would limit compliance with study requirements.
Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
Prior treatment with cabozantinib
Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
Corrected QT (QTc) = QT / ∛RR
QT: duration of QT interval RR: duration of RR interval
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.
Primary purpose
Allocation
Interventional model
Masking
35 participants in 1 patient group
Loading...
Central trial contact
University of California Irvine Medical; Chao Family Comprehensive Cancer Center University of California, Irvine
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal