Unresectable hepatocellular carcinoma (HCC) MedDRA version: 13.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Nemorubicin hydrochloride, 500µg vial
Product Code: PNU-152243A
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN:
Sponsors
Nerviano Medical Sciences S.r.l.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Presence of unresectable, microscopically confirmed HCC, not amenable to any ablation, either newly diagnosed or relapsing after prior surgery, or other prior ablative techniques, or other prior anticancer therapy for HCC, provided that the lesion(s) present at study entry are vascularized through hepatic artery. If biopsy is contraindicated, computerized tomography (CT) or magnetic resonance imaging (MRI) evidence of hepatic tumor and an AFP level of =400 ng/mL will be accepted as evidence of HCC. 2. Intermediate risk population Advanced risk population Tumor staging CLIP 0-1 Tumor staging CLIP 2 bilirubin =1.5 x UNL bilirubin =2.5 mg/dL no portal vein thrombosis portal vein thrombosis admitted Child A or B Child A or B 3. Prior systemic or locoregional anticancer therapy for HCC is allowed, provided that a minimum of 6 weeks have elapsed between the end of prior therapy for HCC and the entry into the study. 4. At least one bidimensionally measurable disease that is =2 cm in at least 1 diameter with conventional CT scan or MRI or =1 cm in at least 1 diameter with spiral CT scan. (For Phase II only) 5. Resolution of all acute toxic effects of any prior surgical procedure or other prior therapy for HCC to NCI CTC Grade =1 6. Age =18 yrs of age and =75 yrs of age. 7. Intermediate risk population: ECOG performance status of 0 or 1. Advanced risk population: ECOG performance status of 1 or 2. 8. Life expectancy of at least 12 weeks. 9. Laboratory data at study entry as specified Absolute neutrophil count (ANC) = 1,500/mm3 (= CTC Grade 1) Platelets = 75,000/mm3 (= CTC Grade 1) Hemoglobin = 10.0 g/dL (= CTC Grade 1) Creatinine = 1.5 x UNL (=CTC Grade 1) Creatinine clearance > 30 mL/min (Cockcroft formula) ALT = 2.5 x ULN (= CTC Grade 1) AST= 2.5 x ULN (= CTC Grade 1) Alkaline phosphatase = 2.5 x ULN (= CTC Grade 1) Partial thromboplastin time (APTT) =1.5 x ULN (= CTC grade 1) Prothrombine time (PT) =1.5 x UNL (= CTC grade 1) INR > 1-1.5 xUNL (= CTC grade 1) Left ventricular ejection fraction (LVEF) - Within normal institutional limits Pregnancy test for females of childbearing potential - Negative within 7 days of starting treatment 10. Signed and dated informed consent document indicating that the patient (or legally acceptable representative or witness in case of oral consent) has been informed of all pertinent aspects of the trial and he/she is able to comply with the treatment plan, scheduled clinic visits, laboratory tests, oncologic tests, and other study procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Histologic classification of HCC, fibrolamellar variant. 2. Current enrollment in another clinical trial. 3. Patients with vascular invasion (in particular, with complete obstruction of the portal vein) as documented by imaging techniques (for intermediate risk population only). 4. Patients with extra-hepatic spread. 5. Administration of any prior systemic or intra-arterial anticancer therapy for HCC containing platinum derivatives. 6. Prior liver transplantation. 7. Administration of any prior radiotherapy to treat the tumor lesion(s) present at study entry. 8. Extrahepatic metastatic disease including known brain or leptomeningeal disease (baseline CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system metastases). 9. No longer applicable. 10. Presence of clinically detectable ascites or pleural effusions 11. Recent bleeding (within prior 6 months) from esophageal varices. 12. Symptomatic ulceration of the gastric or duodenal mucosa = 30 days prior to enrollment. 13. Any known bleeding diathesis. 14. Failure of angiography due to anatomical or technical reasons (see Section 9.2) 15. Currently active second malignancy, other than non-melanoma skin cancers and /or cone-biopsied in situ carcinoma of the cervix uteri. Patients with other malignancies must have been disease free for =2 years. 16. Any of the following in the past within the last year: myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other significant thromboembolic event. 17. Any prior history of symptomatic congestive heart failure. 18. Irreversible cardiac arrhythmias requiring permanent medication or uncontrolled arterial hypertension (arterial pressure =200/110 mmHg). 19. Active infection other than chronic active hepatitis. Patients with known human immunodeficiency virus (HIV) positivity or acquired-immunodeficiency-syndrome (AIDS)-related illness are not eligible. 20. Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of chemotherapy. Male patients must be surgically sterile or must agree to use effective contraception during the period of chemotherapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. 21. 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. 22. Allergy to the contrast agent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is the evaluation of the antitumor efficacy of the combination nemorubicin hydrochloride (HCl) + cisplatin in adult patients with unresectable HCC. The evaluation of the antitumor efficacy will be in terms of response rate (RR, ie the proportion of patients with confirmed objective tumor response [CR or PR] or tumor downstaging allowing tumor lesion ablation by surgery or other ablative techniques relative to the number of evaluable patients). This objective will be pursued upon: identification during the dose-escalation portion of the trial in the targeted populations of the maximum tolerated dose (MTD), dose limiting toxicities (DLT) and the recommended dose of nemorubicin HCl + cisplatin, and characterization of the qualitative/quantitative profile of toxicity.; Secondary Objective: - Evaluation of tumor response characteristics (including duration of response, time to progression [TTP], and changes in alpha-fetoprotein [AFP] tumor marker levels). Since systemic exposure with IHA therapy is lower than by systemic administration, complementary exploratory investigation of tumor response characteristics in the liver will be performed. - Evaluation of overall survival. - Evaluation of safety of repeated administrations of the combo nemorubicin + cisplatin. - Evaluation of the pharmacokinetic profile of nemorubicin and cisplatin, when the two drugs are given in combination. ; Primary end point(s): Dose-escalation portion: - First cycle DLTs to be used for MTD identification. - Laboratory and clinical safety parameters (including cardiac function monitoring). - Adverse events emerging during the trial. Phase II portion: Overall Confirmed Objective Tumor Response: defined as a best confirmed response of CR or PR, or a tumor downstaging allowing for | — |
Countries
France, Germany, Italy, United Kingdom
Outcome results
None listed