Phase 2
N=224
Axitinib For The Treatment Of Advanced Hepatocellular Carcinoma
Hepatocellular Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT01210495 ↗Enrolled (actual)
224
Serious AEs
40.8%
Results posted
May 2015
Primary outcome: Primary: Overall Survival (OS) - Stratified Analysis, Randomized Portion — 12.7; 9.7 months — p=0.2872
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Axitinib (AG-013736) (Drug); Best Supportive Care (Other); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Mar 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) - Stratified Analysis, Randomized Portion |
12.7; 9.7 | 0.2872 |
| SECONDARY Progression-Free Survival (PFS) - Stratified Analysis, Randomized Portion |
3.6; 1.9 | 0.0039 sig |
| SECONDARY Objective Response Rate (ORR) - Percentage of Participants With Objective Response by Stratified Analysis, Randomized Portion |
9.7; 2.9 | 0.0914 |
| SECONDARY Time to Tumor Progression (TTP) - Stratified Analysis, Randomized Portion |
3.7; 1.9 | 0.006 sig |
| SECONDARY Duration of Response (DR) by Unstratified Analysis, Randomized Portion |
6.4; NA | — |
| SECONDARY Percentage of Participants With Overall Clinical Benefit Response (CBR) - Stratified Analysis, Randomized Portion |
31.3; 11.8 | 0.0025 sig |
| SECONDARY Axitinib Steady-State Pharmacokinetic (PK) Parameter - Maximum Observed Plasma Concentration (Cmax), Non-Randomized Portion |
35.74; 21.16 | — |
| SECONDARY Axitinib Steady-State PK Parameter - Area Under the Plasma Concentration Versus Time Curve From 0 to 24 Hour (AUC0-24), Non-Randomized Portion |
310.76; 316.20 | — |
| SECONDARY Axitinib Steady-State Pharmacokinetic Parameter - Time to First Occurrence of Cmax (Tmax), Non-Randomized Portion |
2.50; 1.05 | — |
| SECONDARY Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Clearance (CL/F), Non-Randomized Portion |
32.18; 12.65 | — |
| SECONDARY Axitinib Steady-State Pharmacokinetic Parameter - Terminal Plasma Elimination Half-Life (t1/2), Non-Randomized Portion |
4.12; 4.79 | — |
| SECONDARY Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Volume of Distribution of the Drug During the Elimination Phase (Vz/F), Non-Randomized Portion |
150.01; 81.16 | — |
| SECONDARY Concentration of Soluble Proteins at Baseline in Randomized Portion |
50.67; 50.72; 52313.94; 55430.76; 33.35; 27.23 | — |
| SECONDARY Percentage of Participants With Specific Micro-Ribonucleic Acid (miRNA) Transcript Present in Circulation in Randomized Portion |
100.0; 100.0; 100.0; 100.0; 100.0; 100.0 | — |
| SECONDARY Functional Assessment of Cancer Therapy - Hepatobiliary Questionnaire (FACT-Hep) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
123.33; 135.22 | 0.0006 sig |
| SECONDARY Functional Assessment of Cancer Therapy - General (FACT-G) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
71.20; 78.81 | 0.0014 sig |
| SECONDARY Functional Assessment of Cancer Therapy (FACT)-Hepatobiliary Symptom Index-8 (FHSI-8) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
23.42; 26.69 | <0.0001 sig |
| SECONDARY Functional Assessment of Cancer Therapy-G (FACT-G) Subscales in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
19.39; 23.13; 18.94; 20.21; 17.23; 17.71 | <0.0001 sig |
| SECONDARY Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Subscale (FACT Hep-CS18) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
51.78; 56.74 | 0.0011 sig |
| SECONDARY Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Trial Outcome Index (FACT Hep-TOI) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
87.28; 97.73 | <0.0001 sig |
| SECONDARY Time to Deterioration (TTD) Based on the Composite Endpoint in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
1.9; 1.9 | 0.9182 |
| SECONDARY EuroQoL (EQ-5D)- Health State Profile Utility Score in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
0.67; 0.79 | 0.0024 sig |
| SECONDARY EuroQoL Visual Analogue Scale (EQ-VAS) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model |
68.67; 75.70 | 0.0193 sig |
| SECONDARY Number of Participants With Dose-Limiting Toxicities (DLTs) in Non-Randomized Portion |
2 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) in Non-Randomized Portion |
15; 7; 10; 3; 13; 5 | — |
| SECONDARY Number of Participants With Treatment-Related Adverse Events (AEs) in Non-Randomized Portion |
14; 6; 2; 2; 9; 4 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) in Randomized Portion |
131; 63; 62; 16; 109; 26 | — |
| SECONDARY Number of Participants With Treatment-Related Adverse Events (AEs) in Randomized Portion |
128; 40; 24; 1; 90; 12 | — |
Summary
The study is designed to demonstrate that axitinib plus best supportive care is superior to placebo plus best supportive care in prolonging survival in patients with advanced hepatocellular carcinoma.
Eligibility Criteria
Inclusion Criteria
- Locally advanced or metastatic HCC
- Failure of one prior antiangiogenic therapy including sorafenib, bevacizumab and brivanib.
- Child-Pugh Class A or B (score 7 only) disease.
Exclusion Criteria
- Prior treatment of advanced HCC with more than one prior first-line systemic therapy.
- Any prior local therapy within 2 weeks of starting the study treatment.
- Presence of hepatic encephalopathy and/or clinically relevant ascites.
- Presence of main portal vein invasion by HCC.
Data sourced from ClinicalTrials.gov (NCT01210495). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.