E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with unresectable hepatocellular carcinoma, localized but surgically unresectable or metastatic |
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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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate antitumor activity of continuous sunitinib (Sutent®) treatment in patients with unresectable hepatocellular carcinoma. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of sunitinib (Sutent®) treatment. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacology subproject, final version 2007 05 11 (not conducted in EU) |
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E.3 | Principal inclusion criteria |
1. Histologically, cytologically or radiologically diagnosed HCC, localized but surgically unresectable or metastatic (see appendix 22.3 for radiological criteria).
2. Measurable disease (at least one lesion, outside of pretreated areas, that can be measured in at least one dimension as ≥ 10 mm in spiral/multi-slice CT/MRI according to RECIST).
3. Child-Pugh class A or mildly decompensated Child-Pugh class B liver dysfunction.
4. WHO performance status 0-1 (see appendix 22.4).
5. Adequate hematological values: hemoglobin ≥ 90 g/l, neutrophils ≥ 1.5 x 109/l, thrombocytes ≥ 75 x 109/l.
6. Adequate hepatic function: bilirubin ≤ 2 x ULN, ALAT ≤ 7 x ULN, albumin ≥ 2.5 g/dl.
7. Adequate renal function: creatinine clearance ≥ 40 ml/min (formula Cockroft-Gault see appendix 22.5).
8. Adequate coagulation parameter: Quick ≥ 50 %.
9. Urine dipstick for proteinuria < 2+ or 24 hour urine collection demonstrating ≤ 1 g of protein in 24 hours.
10. Age ≥ 18 years.
11. Women are not breastfeeding, are using effective contraception if sexually active, are not pregnant and agree not to become pregnant during participation in the trial or during the 12 months thereafter. A negative pregnancy test is mandatory for all women < 50 years (unless considered unnecessary by the investigator). Men agree not to father a child during participation in the trial and during the 12 months thereafter.
12. Written informed consent for participation in the trial before registration.
13. Patient compliance and geographic proximity allow proper staging and follow-up.
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E.4 | Principal exclusion criteria |
1. Prior systemic anti-cancer treatment for HCC. The following prior therapies are allowed provided previously treated lesions remain separate from those to be measured in the present trial and previous treatment is completed at least 4 weeks prior to registration: Surgery, Liver-directed therapy (e.g. transarterial embolization/ chemoembolization (limited to 5 treatments), radiofrequency ablation, kryoablation, radiation therapy or percutaneous ethanol injection)
2. Previous malignancy within 5 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer.
3. Prior organ transplantation.
4. Major surgical procedure within 4 weeks before registration.
5. Patients with locally advanced disease who are candidates for radical surgery.
6. Known fibrolamellar HCC or mixed cholangiocarcinoma/HCC.
7. History of hemorrhagic or thrombotic cerebrovascular event in the past 12 months.
8. Documented variceal hemorrhage within 3 months before registration.
9. Requirement of anticoagulant therapy except for low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis (DVT).
10. History or presence of clinically significant acute or unstable cardiovascular, cerebrovascular, renal, gastrointestinal, pulmonary, immunological (with the exception of the presence of hepatitis B virus (HBV), HCV hepatitis (HCV), or cirrhosis), endocrine, or central nervous system disorders.
11. Clinical symptoms or history of CNS metastases or leptomeningeal disease (no imaging required).
12. Clinical ascites (of any grade).
13. Encephalopathy.
14. Known HIV infection.
15. Active infection requiring i.v. antibiotics at registration.
16. Arterial hypertension ≥ 150/100 mmHg despite therapy.
17. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, or atrial fibrillation of any grade, prolongation of QTc > 500 msec in screening electrocardiogram (ECG) or history of familial long QT syndrome.
18. Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to registration.
19. Current use or anticipated need for drugs that are known CYP3A4 inhibitors (ketoconazole, itraconazole, voriconazole, erythromycin and clarithromycin, according to the Swissmedic-approved product information).
20. Current use or anticipated need for drugs that are known CYP3A4 inducers (carbamazepine, continuous treatment with dexamethasone, phenobarbital, phenytoin, rifampicin, and St John’s wort (Johanniskraut), according to the Swissmedic-approved product information). Concurrent antacids are allowed provided they are administered > 1 hour before or > 1 hour after trial drug administration
21. Inability to take oral medications.
22. Psychiatric disorder precluding understanding of information of trial related topics, giving informed consent or interfering with compliance for oral drug intake.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is: 1. Progression free survival (PFS) at 12 weeks
Secondary endpoints are: 2. Objective response 3. Disease stabilization (DS) 4. Duration of DS 5. Progression free survival (PFS) 6. Time to progression (TTP) 7. Overall survival (OS) 8. Adverse events (AEs) 9. Serum alpha fetoprotein (AFP) level
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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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |