A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects with Hepatocellular Carcinoma Who Have Received Prior Sorafenib

Phase 3

Completed

Conditions: livercell cancer
malignant hepatoma
10019815

Registration Number: NL-OMON47199

Lead Sponsor: Exelixis Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

1. Histologische of cytologische diagnose van HCC (resultaten van een voorafgaand biopt wordt geaccepteerd)
2. De proefpersoon heeft een ziekte die niet ontvankelijk is voor een curatieve behandelingsmethode (bv. transplantatie, operatie, radiofrequente ablatie)
3. Eerder behandeld met sorafenib
4. Progressie volgend op tenminste 1 eerdere systemische behandeling voor HCC
5. Herstel tot * graad 1 van toxische effecten van eerdere behandelingen, tenzij de bijwerkingen klinisch niet significant zijn en/of stabiel zijn bij ondersteunende behandeling
6. Leeftijd * 18 jaar op de dag van toestemming
7. ECOG-performancestatus van 0 of 1
8. Adequate hematologische functie, gebaseerd op het voldoen aan de volgende laboratoriumcriteria binnen 7 dagen voor randomisatie:
a. absolute aantal neutrofielen (ANC) * 1200/mm3 (* 1,2 x 109/l)
b. bloedplaatjes * 60.000/mm3 (* 60 x 109/l)
c. hemoglobine * 8 g/dl (* 80 g/l)
9. Adequate nierfunctie, gebaseerd op het voldoen aan de volgende laboratoriumcriteria binnen 7 dagen voor randomisatie:
a. serumcreatinine * 1,5 x de bovengrens van normaal of een berekende creatinineklaring * 40 ml/min (gebruikmakend van de Cockroft-Gault-vergelijking: (140 * leeftijd) x gewicht (kg)/(serumcreatinine × 72 [mg/dl]) voor mannen. (Voor vrouwen vermenigvuldigen met 0,85.)
EN
b. urinaire eiwit/creatinine-verhouding (*urine protein/creatinine ratio*, UPCR) * 1 mg/mg (* 113,1 mg/mmol) of eiwit in 24-uurs urine < 1 g
10. Child-pughscore A
11. Totaal bilirubine * 2 mg/dl (* 34,2 µmol/l) binnen 7 dagen voor randomisatie
12. Serumalbumine * 2,8 g/dl (* 28 g/l) binnen 7 dagen voor randomisatie
13. Alanineaminotransferase (ALAT) en aspartaataminotransferase (ASAT) < 5,0 x de bovengrens van normaal (*upper limit of normal*, ULN) binnen 7 dagen voor randomisatie
14. Hemoglobine A1c (HbA1c) * 8% binnen 7 dagen voor randomisatie
(als HbA1c resultaten niet beschikbaar zijn [bv, hemoglobine variant], een nuchtere serum glucose * 160 mg/dL)
15. Antivirale therapie volgens de plaatselijke zorgstandaard in geval van actieve infectie met hepatitis B-virus (HBV)

Exclusion Criteria

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.
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 least 7 days before randomization. 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 including but not limited to :
inferior vena cava, pulmonary artery, or aorta). Subjects with lesions
invading the portal vasculature are eligible.
f. Clinically significant bleeding risk including the following within 3 months of randomization: hematuria, hematemesis, hemoptysis of >0.5 teaspoon (>2.5 mL) of red blood, o

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint: Overall survival (OS)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br>* Objective response rate (ORR) per RECIST 1.1<br /><br>* Progression-free survival (PFS) per RECIST 1.1<br /><br><br /><br>Additional endpoints:<br /><br>* Safety and tolerability<br /><br>* Pharmacokinetics (PK)<br /><br>* Relationship of baseline and changes in biomarkers with treatment and/or<br /><br>clinical outcome<br /><br>* Health-related quality of life (HRQOL) as assessed by the EuroQol Health<br /><br>questionnaire instrument (EQ-5D-5L)</p><br>

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A Phase 3, Randomized, Double-blind, Controlled Study of Cabozantinib (XL184) vs Placebo in Subjects with Hepatocellular Carcinoma Who Have Received Prior Sorafenib

Recruitment & Eligibility

Study & Design

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