Phase 2
Completed N=102
E7050 in Combination With Sorafenib Versus Sorafenib Alone as First Line Therapy in Participants With Hepatocellular Carcinoma
Source: ClinicalTrials.gov NCT01271504 ↗Enrolled (actual)
102
Serious AEs
44.9%
Results posted
Apr 2021
Primary outcomePrimary: Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT) — 1; 2 Participants
Summary
The purpose of this study is to determine whether patients with hepatocellular carcinoma who receive either E7050 administered with Sorafenib or Sorafenib alone experience greater benefit (cancer responds to treatment) when E7050 is administered with Sorafenib.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b: Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT) |
1; 2 | — |
| PRIMARY Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day -7 |
1330; 2320 | — |
| PRIMARY Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1 |
1820; 2820 | — |
| PRIMARY Phase 1b: Cmax: Maximum Observed Plasma Concentration for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1 |
2140; 4570 | — |
| PRIMARY Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day -7 |
2; 2.38 | — |
| PRIMARY Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1 |
3; 3.53 | — |
| PRIMARY Phase 1b: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1 |
2.98; 5.01 | — |
| PRIMARY Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day -7 |
30400; 47200 | — |
| PRIMARY Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 1 Cycle 1 |
24000; 36800 | — |
| PRIMARY Phase 1b: AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t Over the Dosing Interval for Golvatinib When Administered in Combination With Sorafenib at Day 28 Cycle 1 |
35300; 68700 | — |
| PRIMARY Phase 1b: t1/2: Terminal Elimination Half-life for Golvatinib When Administered in Combination With Sorafenib at Day -7 |
38.1; 35.9 | — |
| PRIMARY Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
42; 40; 20; 17 | — |
| PRIMARY Phase 2: Number of Participants With AEs by Severity Grades |
0; 2; 4; 6; 24; 25 | — |
| PRIMARY Phase 2: Number of Participants With Adverse Events Related to Vital Signs |
2; 0 | — |
| PRIMARY Phase 2: Number of Participants With Clinically Significant Change From Baseline in Blood Pressure Including Systolic and Diastolic Blood Pressures |
0; 0 | — |
| PRIMARY Phase 2: Number of Participants With Worst Shifts Post Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG-PS) |
7; 4; 3; 7; 3; 0 | — |
| PRIMARY Phase 2: Number of Participants With Clinically Significant Change From Baseline in Laboratory Values |
0; 0 | — |
| PRIMARY Phase 2: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters |
0; 0 | — |
| SECONDARY Phase 2: Time to Progression (TTP) |
10.29; 16.00 | — |
| SECONDARY Phase 2: Progression Free Survival (PFS) |
10.29; 15.57 | — |
| SECONDARY Phase 2: Percentage of Participants With PFS at Week 12 |
47.4; 57.5 | — |
| SECONDARY Phase 2: Overall Survival (OS) |
27.86; 37.71 | — |
| SECONDARY Phase 2: Percentage of Participants With Overall Response |
4.8; 4.8 | — |
Eligibility Criteria
Inclusion Criteria
- Unresectable locally advanced or metastatic HCC;
- Histologic confirmation not required if other diagnostic criteria are met;
- No previous systemic anti-cancer therapy permitted (2 prior systemic anti-cancer regimen are allowed in Phase Ib). Previous chemoembolization, radioembolization, radiofrequency ablation, or other local ablative therapies are permitted if greater than 6 weeks of first day of study-defined treatment;
- ECOG PS 0 or 1; Child-Pugh Cirrhotic Status A or B with a score of 7;
- Blood pressure must be well-controlled (less than or equal to 140/90 mmHg at screening) with or without antihypertensive medication. Patients must have no history of hypertensive crisis or hypertensive encephalopathy;
Exclusion Criteria
- Previously received E7050 anti-cmet, or anti-angiogenic therapy (prior anti-angiogenic therapy is permitted in Phase Ib only);
- Presence of brain metastases, unless the patient has received adequate treatment at least 4 weeks prior to randomization, and is stable, asymptomatic, and off steroids for at least 4 weeks prior to randomization;
- Palliative radiotherapy is not permitted throughout the study period;
- Active hemoptysis
- Serious non-healing wound, ulcer, or active bone fracture;
- Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to commencing study treatment, or anticipation of need for a major surgical procedure during the course of the study;
- Clinically significant gastrointestinal bleeding (bleeding requiring procedural intervention, eg. variceal banding, transjugular intrahepatic portosystemic shunt (TIPS) procedure, arterial embolization, topical coagulation therapy) within 6 months prior to first dose.
Data sourced from ClinicalTrials.gov (NCT01271504). 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. Informational only — not medical advice.