Clinical Trials List
Protocol NumberA8471005
2014-03-15 - 2017-12-31
Phase II
Terminated2
Study ended1
ICD-10C22.0
Liver cell carcinoma
ICD-9155.0
Malignant neoplasm of liver, primary
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
-
Trial Applicant
台灣法瑪特股份有限公司
-
Sponsor
PFIZER
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- JA-DER LIANG Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Shang-Wen Chen Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
- Shang-Hung Chen Division of Hematology & Oncology
- 林明賢 Division of Hematology & Oncology
- 黃文聰 Division of Hematology & Oncology
- 陳威宇 Division of Hematology & Oncology
- 陳昭勳 Division of Hematology & Oncology
- 林建良 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 陳昇弘 Digestive System Department
- Hung-Yao Chen Digestive System Department
- Cheng-Yuan Peng Digestive System Department
- 蘇文邦 Digestive System Department
- Po-Heng Chuang Digestive System Department
- Hsueh-Chou Lai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Study ended
Condition/Disease
Advanced Hepatocellular Carcinoma
Objectives
Primary objective: To determine whether overall survival (OS) of PF-03446962 plus best
supportive care (BSC) is superior to OS of BSC in patients with advanced HCC following
sorafenib failure
Secondary objectives:
To compare measures of tumor control between treatment arms;
To evaluate the safety and tolerability of PF-03446962 administered in combination
with BSC;
To assess the potential influence on PF-03446962 efficacy of gene alterations,
transcripts and proteomic profiles related to ALK-1 signaling and HCC biology in
patients’ tumor (pre-randomization biopsy in all patients) and blood samples;
To assess biomarkers associated with tumor resistance mechanisms and/or tumor
progression in HCC patients treated with PF-03446962 who have experienced
objective response or SD for at least 16 weeks from randomization and have then
experienced disease progression on or after study treatment (in Arm A only);
To evaluate the pharmacokinetic profile of PF-03446962 in patients with HCC; and to
assess the potential relationship between serum concentrations (maximum serum
concentration and/or trough serum concentration) at steady state and safety,
biomarker, and efficacy parameters;
To evaluate the immunogenicity of PF-03446962;
To compare patients’ health-related quality of life (HRQoL) and health status
between both arms.
Test Drug
PF-03446962 injection
Active Ingredient
PF-03446962
Dosage Form
Injection
Dosage
100mg/10mL
Endpoints
Primary endpoint: Overall Survival (OS)
Secondary endpoints:
Time to Progression (TTP), Progression Free Survival (PFS), Objective Response
Rate (ORR), Duration of Response (DR) and Disease Control Rate (DCR) at
16 weeks [by Response Evaluation Criteria in Solid Tumor (RECIST 1.1)];
Adverse Events as characterized by type, frequency, severity (as graded by
NCI CTCAE v.4.0), timing, seriousness and relationship to study therapy;
Laboratory abnormalities as characterized by type, frequency, severity (as graded by
NCI CTCAE v. 4.0) and timing;
Tumor molecular characteristics including but not limited to transcriptomic (RNA)
signatures of efficacy. Genes alterations studied may include but are not limited to
TGF-β. Somatic DNA mutations, and expression of proteins associating with
sensitivity and resistance may also be assessed; levels of circulating proteins
including but not limited to angiogenesis and HCC biology;
Observed maximum serum concentration (Cmax) and serum trough concentrations
(Ctrough);
Human Anti-Human Antibodies (HAHA);
Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire
(FACT-Hep).
Secondary endpoints:
Time to Progression (TTP), Progression Free Survival (PFS), Objective Response
Rate (ORR), Duration of Response (DR) and Disease Control Rate (DCR) at
16 weeks [by Response Evaluation Criteria in Solid Tumor (RECIST 1.1)];
Adverse Events as characterized by type, frequency, severity (as graded by
NCI CTCAE v.4.0), timing, seriousness and relationship to study therapy;
Laboratory abnormalities as characterized by type, frequency, severity (as graded by
NCI CTCAE v. 4.0) and timing;
Tumor molecular characteristics including but not limited to transcriptomic (RNA)
signatures of efficacy. Genes alterations studied may include but are not limited to
TGF-β. Somatic DNA mutations, and expression of proteins associating with
sensitivity and resistance may also be assessed; levels of circulating proteins
including but not limited to angiogenesis and HCC biology;
Observed maximum serum concentration (Cmax) and serum trough concentrations
(Ctrough);
Human Anti-Human Antibodies (HAHA);
Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire
(FACT-Hep).
Inclution 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); Adequate renal function (including serum
creatinine 1.5 x ULN, or creatinine clearance 60 ml/min as per institution
standard);
11. INR <1.7 or prothrombin time (PT) prolongation < 4 seconds* above ULN;
12. Adequate liver function (including AST/ALT 5.0 x ULN; total serum bilirubin
2 mg/dL*; and serum albumin ≥ 2.8 g/d**) [See Appendix 1: Child-Pugh Score
1* or 2** ];
13. Prior liver transplantation is permitted; immunosuppressive agents in transplanted
patients are also allowed
14. Male and female patients of childbearing potential, must agree to use a highly
effective method of contraception throughout the study and for 6 months after the last
dose of assigned treatment. A subject is of childbearing potential if, in the opinion of
the investigator, he/she is biologically capable of having children and is sexually
active;
15. Evidence of a personally signed and dated informed consent document indicating that
the patient (or a legal representative) has been informed of all pertinent aspects of the
study;
16. Patients who are willing and able to comply with scheduled visits, treatment plans,
laboratory tests and other study procedures.
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); Adequate renal function (including serum
creatinine 1.5 x ULN, or creatinine clearance 60 ml/min as per institution
standard);
11. INR <1.7 or prothrombin time (PT) prolongation < 4 seconds* above ULN;
12. Adequate liver function (including AST/ALT 5.0 x ULN; total serum bilirubin
2 mg/dL*; and serum albumin ≥ 2.8 g/d**) [See Appendix 1: Child-Pugh Score
1* or 2** ];
13. Prior liver transplantation is permitted; immunosuppressive agents in transplanted
patients are also allowed
14. Male and female patients of childbearing potential, must agree to use a highly
effective method of contraception throughout the study and for 6 months after the last
dose of assigned treatment. A subject is of childbearing potential if, in the opinion of
the investigator, he/she is biologically capable of having children and is sexually
active;
15. Evidence of a personally signed and dated informed consent document indicating that
the patient (or a legal representative) has been informed of all pertinent aspects of the
study;
16. Patients who are willing and able to comply with scheduled visits, treatment plans,
laboratory tests and other study procedures.
Exclusion Criteria
Patients presenting with any of the following will not be included in the study:
1. Prior systemic treatment for advanced HCC other than 1
st
-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;
11. Other severe acute or chronic medical or psychiatric condition (including recent
[within the past year] or active suicidal ideation or behavior) or laboratory
abnormality that may increase the risk associated with study participation or
investigational product 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;
12. Patients who are investigational site staff members directly involved in the conduct of
the trial and their family members, site staff members otherwise supervised by the
Investigator, or patients who are Pfizer employees directly involved in the conduct of
the trial;
13. History of any other malignancy in the previous 3 years (except for local cancers
resected with curative intent without evidence of recurrence over the past 12 months);
1. Prior systemic treatment for advanced HCC other than 1
st
-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;
11. Other severe acute or chronic medical or psychiatric condition (including recent
[within the past year] or active suicidal ideation or behavior) or laboratory
abnormality that may increase the risk associated with study participation or
investigational product 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;
12. Patients who are investigational site staff members directly involved in the conduct of
the trial and their family members, site staff members otherwise supervised by the
Investigator, or patients who are Pfizer employees directly involved in the conduct of
the trial;
13. History of any other malignancy in the previous 3 years (except for local cancers
resected with curative intent without evidence of recurrence over the past 12 months);
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
180 participants
