A study comparing E7050 and Sorafenib to Sorafenib alone for the treatment of liver cancer

Phase 1

• Conditions: Hepatocellular carcinoma; MedDRA version: 14.1 Level: LLT Classification code 10049010 Term: Carcinoma hepatocellular System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-000752-41-GB
• Lead Sponsor: Eisai Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-10-04
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 95

Inclusion Criteria

Patients may be entered in the study only if they meet all of the following criteria:

1. Male or female patient = 18 years of age;

2. Histologically or cytologically confirmed, unresectable locally advanced or metastatic HCC. Patients with HCC may be enrolled without histological confirmation of disease so long as they meet the following criteria for diagnosis of HCC (and all other protocol eligibility criteria):
Lesion >2 cm in diameter, AND
Serum a-fetoprotein (AFP) =400 ng/mL (if serum AFP is <400 ng/mL,
a biopsy is required to confirm HCC); AND
Radiological appearance of mass is suggestive of HCC (ie, contrast enhanced CT or MRI with arterial hypervascularity AND venous or delayed phase washout);

3. No previous prior systemic anti-cancer therapy (2 prior systemic anti-cancer regimens are allowed in Phase 1b);

4. At least 1 site of measurable disease by the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v. 1.1) criteria. Tumor lesions previously treated with local therapy should demonstrate clear dimensional increase by radiographic assessment in order to be selected as target lesion(s) at Baseline;

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1;

6. Child-Pugh Cirrhotic Status A or B with a score of 7;

7. For patients with hypertension, it must be well controlled. If a patient presents with poorly controlled hypertension, defined as a mean systolic blood pressure =140 mm Hg or mean diastolic blood pressure =90 mm Hg, antihypertensive medication(s) should be initiated or adjusted with a goal to control the blood pressure <140/90 mm Hg. Blood pressure must be reassessed on 2 occasions, consecutively, that are separated by a minimum of 24 hours;

8. Patients must have adequate liver function as evidenced by bilirubin =2.0 mg/dL and alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =5 times the upper limit of the normal range (ULN). If there are bone metastases, liver-specific alkaline phosphatase (gamma-glutamyltransferase) may be separated from the total and used to assess liver function instead of total alkaline phosphatase;

9. International normalized ratio (INR) 0.8 to 1.4 or =3 for patients receiving vitamin K antagonists;

10. Patients must have adequate renal function as evidenced by:
Serum creatinine =1.5 X ULN and/or creatinine clearance >50 mL/min
per the Cockcroft and Gault formula;
Urine protein creatinine (UPC) ratio of <1 on a spot urine or <1.0 g
of protein determined by 24-hour urine protein analysis. If the UPC
ratio is =1, 24-hour urine protein must be assessed and the 24-
hour urine protein must be <1.0 g of protein for the patient to be
eligible;

11. Patients must have adequate bone marrow function as evidenced by an absolute neutrophil count (ANC) =1.5 X 109/L, hemoglobin =9.0 g/dL (a hemoglobin <9.0 g/dL at Screening is acceptable if

Exclusion Criteria

Patients will not be entered in the study for any of the following reasons:

1. Prior treatment with E7050, its chemical derivatives or prior anti-c-Met therapy;

2. Prior anti-angiogenic therapy (permitted in Phase Ib);

3. Prior systemic anti-cancer therapy (2 prior systemic anti-cancer therapies are allowed for the Phase 1b portion of the study, must not be within 4 weeks prior to first day of study-defined treatment);

4. Prior external beam radiation to the primary site;

5. Prior central thoracic radiation therapy, including to the heart;

6. Previous chemoembolization, radioembolization, radiofrequency ablation, or other local ablative therapies within 6 weeks prior to the first day of study-defined treatment;

7. Child-Pugh Cirrhotic Status >7;

8. History of other malignancies except: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated, a) in situ carcinoma of the uterine cervix, or b) prostate cancer, or c) superficial bladder cancer; or (3) other curatively treated solid tumor with no evidence of disease for =3 years;

9. 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;

10. Received treatment in another clinical study within the 30 days prior to commencing study treatment or patients who have not recovered from side effects of an investigational drug to Grade =1, except for peripheral neuropathy (Grade 1 and Grade 2 are permitted) and alopecia;

11. Palliative radiotherapy is not permitted throughout the study period;

12. Common Terminology Criteria (CTC) Grade =3 peripheral neuropathy (Grade 1 and Grade 2 are permitted);

13. Active clinically serious infections defined as Grade =3 according to CTCAE v. 4.0;

14. Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury within the 28 days prior to commencing study treatment. Minor surgery such as core biopsy or Portacath placement or skin biopsy is permitted if =7 days have passed;

15. History of bleeding diathesis or coagulopathy other than due to anti-coagulation therapy;

16. History of bleeding varices;

17. Active hemoptysis (defined as bright red blood of ½ teaspoon or more) within the 30 days prior to study entry;

18. Clinically significant gastrointestinal bleeding (bleeding requiring procedural intervention, eg. variceal banding, transjugular intrahepatic portosystemic shunt procedure, arterial embolization, topical coagulation therapy) within 6 months prior to first dose;

19. History of untreated deep venous thrombosis within the past 6 months (eg, calf vein thrombosis);

20. R

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified