Advanced hepatocellular carcinoma
Conditions
Sponsors
Takeda Pharmaceutical Company Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female Japanese participants 20 years of age or older on the day of consent. 2. Histological or cytological diagnosis of HCC (results of a previous biopsy will be accepted). 3. Measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the investigator. 4. Participants who have disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation). 5. Participants who have received 1 or 2 prior anticancer therapies for advanced HCC. - Cohort A: participants who have received prior sorafenib. - Cohort B: participants who have not received prior sorafenib. Note: Additional prior systemic therapies used as adjuvant or local therapy are allowed. 6. Radiographic progression following prior systemic anticancer therapy for advanced HCC. 7. Recovery to ==1,200/mm^3. b) Platelets >=60,000/mm^3. c) Hemoglobin >=8 g/dL. d) Serum creatinine ==40 mL/min using the Cockroft-Gault equation. e) Urine protein-to-creatinine ratio (UPCR) ==2.8 g/dL. h) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<5.0 x ULN. i) Hemoglobin A1c (HbA1c) =<8% (if HbA1c results are unavailable [eg, hemoglobin variant], a fasting serum glucose =<160 mg/dL). 11. Antiviral therapy per local standard of care if active hepatitis B virus (HBV) infection. 12. Female participants who: a) Are postmenopausal (natural amenorrhea, not due to other medical reasons) for at least 1 year before the Screening visit, OR b) Are surgically sterile, OR c) If they are of childbearing potential, agree to practice 1 highly effective method of birth control with a condom, which is an effective barrier method of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, OR d) Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, from the time of signing the informed consent through 4 months after the last dose of study drug. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], condoms only, withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception.) Male participants, even if surgically sterilized (ie, status postvasectomy), who: e) Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug. If their partner are of childbearing potential, their female partner should use 1 highly effective method of birth control at the same time, OR f) Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, from the time of signing the informed consent through 4 months after the last dose of study drug. (Periodic abstinence [e
Exclusion criteria
Exclusion criteria: 1. Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma. 2. Any type of anticancer agent within 14 days before the first day of study drug administration (Week 1 Day 1). 3. Radiation therapy within 28 days (14 days for radiation for bone metastases) or radionuclide treatment (eg, I-131 or Y-90) within 42 days before Week 1 Day 1 (participant is excluded if there are any clinically relevant ongoing complications from prior radiation therapy). 4. Prior Cabozantinib treatment. 5. Treatment with any investigational products (excluding anticancer products approved in Japan) within 28 days before Week 1 Day 1. 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 Week 1 Day 1. Eligible participants must be without corticosteroid treatment at Week 1 Day 1. 7. Concomitant anticoagulation, with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Note: Low-dose aspirin for prophylactic use (per local applicable guidelines) and low-dose, low molecular weight heparins (LMWH) are permitted (LMWH has not been approved for the use for cardioprotection in Japan). Anticoagulation with therapeutic doses of LMWH is allowed in participants without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before Week 1 Day 1, and who have had no complications from a thromboembolic event or the anticoagulation regimen. 8. Participants who have 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 blood pressure (BP) >150 mm Hg systolic, or >100 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event within 6 months before Week 1 Day 1. iv. Thromboembolic event within 3 months before Week 1 Day 1. v. A left-ventricular ejection fraction =<50%. 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 Week 1 Day 1. Note: Complete healing of an intra-abdominal abscess must be confirmed prior to Week 1 Day 1. c) Major surgery within 2 months before Week 1 Day 1. Complete healing from major surgery must have occurred 1 month before Week 1 Day 1. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before Week 1 Day 1. Participants 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 including, but not limited to: inferior vena cava, pulmonary artery, or aorta. Participants with invasion or thromboses of portal/hepatic vasculature attributed t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy 24-Week Progression-Free Survival Rate (PFSR) Timeframe; Week 25 Day 1 plus 7 days 24-week PFSR= percentage of participants with progression-free survival (PFS) at least 24 weeks at Week 25 Day 1 plus 7 days. PFS= time from the first day of study drug administration to the earlier of progressive disease (PD) or death due to any cause per RECIST 1.1. PD= at least a 20% increase in the sum of target lesion diameters (SoD) with reference to smallest (nadir) SoD. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. For nontarget lesion time Point Response, unequivocal progression of nontarget lesions. A modest 'increase' in size of one or more nontarget lesions is usually not sufficient to quality for unequivocal progression status,it must not be representative of a single lesion increase. A lesion identified in an anatomical location that was not scanned at baseline is considered a new lesion. Lesion qualifies as PD if finding is unequivocally not due to change in imaging technique or modality. | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Progression-Free Survival (PFS) Timeframe; Until disease progression, or death or end of study (Up to approximately 3 years) PFS was defined as time from the first day of study drug administration to the earlier of PD per RECIST 1.1 as assessed by IRC or death due to any cause. Per RECIST 1.1, for target lesion time point response, PD was defined at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. For nontarget lesion time point response, unequivocal progression of nontarget lesions. A modest 'increase' in the size of one or more nontarget lesions is usually not sufficient to quality for unequivocal progression status. It must be representative of overall disease status change, not a single lesion increase. The lesion qualifies as a PD if the finding is unequivocally not due to a change in the imaging technique or modality efficacy Objective Response Rate (ORR) Timeframe; Up to approximately 2 years ORR was defined as the percentage of participants whose best overall response was complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by IRC, which was confirmed by a subsequent evaluation conducted >= 28 days later. Per RECIST 1.1, for target lesion time point response, CR was defined disappearance of all target lesions. All pathological lymph nodes (whether target or nontarget) must have reduction in short axis to =28 days later, and SD have to be maintained for at least 8 weeks after first day of study drug administration. CR= disappearance of all target lesions. All pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. For nontarget lesion time point response, disappearance of all nontarget lesions. All lymph nodes must be nonpathological in size (<10 mm short axis); PR= as at least a 30% decrease i | — |
Countries
Japan
Outcome results
None listed