A phase 2, randomized, open label study to evaluate the efficacy, safety, pharmacodynamics, pharmacokinetics of the anti-ALK-1 MAB PF-03446962 in combination with best supportive care vs. best supportive care alone in adult patients with advanced hepatocellular carcinoma.

Pfizer Inc, 235 East 42nd Street, New York, NY 100170 sites180 target enrollmentApril 10, 2014

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Not specified
Sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
Enrollment: 180
Status: Active, not recruiting
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

April 10, 2014

End Date

TBD

Last Updated

10 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Eligibility Criteria

Inclusion Criteria

•1\. Diagnosis of locally advanced or metastatic HCC, obtained by histology/cytology (on a prior tumor biopsy) or by imaging (acceptable imaging modalities include triphasic contrast\-enhanced helical CT, triphasic dynamic contrast\-enhanced MRI and contrast\-enhanced ultrasonography); all patients must provide one archival tumor specimen (if collected at the time of primary diagnosis and still available).
•2\. HCC not amenable to local therapy.
•3\. Documented progression on or after treatment with sorafenib. Patients who withdrew from sorafenib due to intolerance are eligible provided that they had disease progression and did not receive any anti\-cancer therapy after the last sorafenib dose. Sorafenib failure must be confirmed by the Investigator upon review of appropriate imaging documentation. Imaging documentation of sorafenib failure must be retained at the site by the Investigator for potential retrospective independent central review; before randomization, all patients must provide a de novo tumor block obtained after disease progression on sorafenib (pre\-randomization de novo biopsy). Inability to obtain this biopsy will make the patient ineligible for the study
•4\. Measurable or non\-measurable disease according to RECIST v. 1\.1\.
•5\. Child\-Pugh Class A disease (see Appendix 1\). Score for hepatic encephalopathy must be 1; ascites score must be \= 2\.
•6\. At least 2 weeks since completion of prior radiotherapy, or surgical procedure (4 weeks for major surgery).
•7\. All prior treatment\-related toxicities must have resolved to baseline severity or CTCAE Grade \=1 except for alopecia or other AEs not constituting a safety risk for the patients by investigator’s judgement.
•8\. Age \=18 years (or \=20 years for Japanese patients).
•9\. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) must be 0 or 1\.
•10\. Adequate bone marrow function (including ANC \=1,500/mm3; Platelets \= 75,000/mm3; Hemoglobin \=9 g/dL).

Exclusion Criteria

•1\. Prior systemic treatment for advanced HCC other than 1st\-line sorafenib (single agent or in combination).
•2\. Prior local therapy (such as hepatic arterial embolization, TACE, hepatic arterial infusion, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 2 weeks of starting the study treatment.
•3\. Presence of main portal vein invasion by HCC (invasion to 1st or 2nd branch of portal vein is acceptable).
•4\. Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are radiographically and neurologically stable.
•5\. Clinically significant bleeding disorders, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis or melena in the past 3 months; or untreated high risk esophageal varices in patients with known portal hypertension.
•6\. History of Osler\-Weber\-Rendu syndrome or Hereditary Hemorrhagic Telangiectasia.
•7\. Known active and clinically significant bacterial, fungal or viral infection (other than hepatitis B (HBV), hepatitis C (HCV)), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)\-related illness.
•8\. Any one of the following currently or in the previous 6 months: myocardial infarction, congenital long QT syndrome, torsades de points, clinically significant ventricular arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF NY Heart Association class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism; as well as bradycardia defined as \<50 bpms. Ongoing cardiac dysrrhythmias of CTCAE Grade \=2, atrial fibrillation of any grade, or QTc interval \>480 msec (unless considered not clinically significant) at screening are exclusionary.
•9\. Pregnant females; breastfeeding females; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for 6 month after last dose of investigational product.
•10\. Participation in other studies involving investigational drugs (Phases 1\-4\) within 1 month before the current study begins and/or during study participation.