E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Hepatocellular carcinoma (HCC) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate Overall Survival |
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E.2.2 | Secondary objectives of the trial |
To investigate antitumor activity (progression-free survival [PFS] Time to Tumor Progression [TTP]) > To assess the adverse event profile and tolerability of TAC 101 as second line treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Male or female patients who meet all of the following criteria are eligible for enrollment in the study: 1. Provide written informed consent prior to performance of any study procedures; 2. Is at least 18 years of age; 3. Have a diagnosis of advanced unresectable histologically confirmed HCC (excluding fibrolamellar carcinoma); 4. Have discontinued from first line treatment with sorafenib monotherapy for any reason (ie, tumor disease progression, intolerance) at least 14 days prior to planned randomization but have not received any second line treatment for HCC; 5. Have recovered from any significant sorafenib-related treatment toxicities prior to randomization (≤Grade 1); 6. Have at least 1 target lesion that is viable (has vascularization) and can be accurately measured according to RECIST; 7. Patients who have received local therapy prior to sorafenib administration (radiation, surgery, hepatic arterial embolization, chemoembolization, RFA, percutaneous ethanol injection [PEI] or cryoablation) are eligible. Local therapy must be completed at least 4 weeks prior to the baseline scan; 8. Have ECOG score of 0, 1, or 2; 9. Child-Pugh score <8; 10. Have adequate organ function defined as: a. Platelet count ≥50 × 109/L; b. Hemoglobin ≥8.0 g/dL; c. Total bilirubin ≤3 mg/dL; d. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN; e. Serum creatinine ≤1.5 × ULN; f. PT-international normalized ratio (INR) ≤2.3 or PT ≤6 seconds above control; g. Total white blood cell (WBC) count ≥2.0 × 109/L; 11. Is able to take medications orally (eg, no feeding tube); and 12. Women of childbearing potential must have a negative pregnancy test (urine or serum) prior to randomization and within 2 days prior to starting the study drug. Females must agree to adequate non-estrogenic birth control if conception is possible during the study; and males must agree to adequate birth control during the study and up to 6 months after the discontinuation of study medication. |
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E.4 | Principal exclusion criteria |
Patients should be excluded from this study if they do not fulfill the inclusion criteria, or if any of the following conditions are observed: 1. History of DVT, PE, myocardial infarction (MI), CVA, transitory ischemic attack (TIA), or any other significant TE during the last 3 years; 2. Have clinically significant symptoms of hepatic encephalopathy or known brain metastasis; 3. Patients who have had clinically significant acute gastrointestinal bleeding as a result of portal vein hypertension within 4 weeks prior to randomization are excluded; however, patients with a history of acute gastrointestinal bleeding that have received appropriate treatment, ie, ligation of varices, are eligible; 4. Are receiving therapeutic regimens of anticoagulants, with the exception of prophylaxis care of indwelling venous access devices; 5. Have received a liver transplant; 6. Are taking prohibited medication as described in Section 7.3; 7. Have received a previous systemic therapy (including investigational agents) other than sorafenib (see Inclusion Criterion 4) for treatment of HCC. Patients participating in surveys or observational studies are eligible to participate in this study; 8. Have had treatment with any of the following within the specified timeframe prior to randomization: a. Any sorafenib within the 14 days prior to randomization; b. Major surgery within the 4 weeks prior to randomization; c. Any transfusion, treatment with blood component preparation, received erythropoietin , albumin preparation, and granulocyte colony-stimulating factor (G-CSF) within the 2 weeks prior to randomization; 9. Has a serious illness or medical condition(s) including, but not limited to the following: a. Known gastrointestinal disorder, including malabsorption, chronic nausea, vomiting, or diarrhea present to the extent that it might interfere with oral intake and absorption of the study medication; b. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness; c. Previous or concurrent malignancy except for basal cell carcinoma and/or in situ carcinoma of the cervix, or other solid tumor treated curatively and without evidence of recurrence for at least 3 years prior to the study; d. Uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain; e. Has active or uncontrolled clinically serious infection excluding chronic hepatitis; f. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study (eg, active urinary tract infection); or g. Known allergy or hypersensitivity of TAC-101 and any other components used in the TAC-101 tablet. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is Overall Survival. Survival is defined as the time from date of randomization to date of death. In the absence of death confirmation or for patients alive at the time of analysis, survival time will be censored at the date of the last study follow-up. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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One interim analysis to test for early demonstration of potential inferior survival rate of the TAC 101 arm (one-sided test for inferiority) is planned. If TAC-101 is proven to be inferior to the placebo, the trial will be stopped. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |