Clinical Trials List
Protocol NumberGW-020202
NCT Number(ClinicalTrials.gov Identfier)NCT03447951
2017-01-01 - 2028-12-31
Phase II
Not yet recruiting2
Recruiting4
ICD-10C22.0
Liver cell carcinoma
A Phase II, Dose-randomization, Open-label Study to Assess the Safety and Efficacy of PTS100 in Primary Hepatocellular Carcinoma Patients Who Are Ineligible for Operation or Current Locoregional Therapy
-
Trial Applicant
A2 HEALTHCARE TAIWAN CORPORATION
-
Sponsor
Gongwin Biopharm Co., Ltd.
-
Trial scale
Taiwan Multiple Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 廖思涵 Digestive System Department
- 吳志宏 Division of Radiology
- Chien-Hung Chen Digestive System Department
- 張智凱 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chien-An Liu Division of Radiology
- Yun-Cheng Hsieh Digestive System Department
- Pei-Chang Lee Digestive System Department
- San-Chi Chen Division of Hematology & Oncology
- I-Cheng Lee Digestive System Department
- Rheun-Chuan Lee Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林俊宇 Division of Radiology
- 夏和雄 Digestive System Department
- Chun-Chao Chang Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 蔡炘儒 Digestive System Department
- 李少武 Digestive System Department
- 張碧倚 Division of Radiology
- 呂宜達 Digestive System Department
- 吳旭 Division of General Surgery
- Sheng-Shun Yang Digestive System Department
- YI-JU CHEN Division of General Surgery
- 詹松儒 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Yi-Chung Hsieh Digestive System Department
- 陳威廷 Digestive System Department
- 呂嘉偉 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Hepatocellular Carcinoma (HCC)
Objectives
Primary objective:
To evaluate the efficacy, measured by objective response rate (ORR) of pooled treatment groups based on the modified RECIST (mRECIST) criteria at concluding visit.
If at least 11/26 evaluable patients achieved objective response, then PTS100 is concluded with objective response rate of at least 50% and is worth further investigation.
Test Drug
PTS100
Active Ingredient
Para-Toluenesulfonamide (PTS)
Dosage Form
Injection
Dosage
330 mg/ml
Endpoints
Primary Endpoint
Objective Response Rate (ORR) at concluding visit:
Target lesion definition (the same as local/treated tumor in
this study):
• The lesion can be classified as a measurable lesion by
modified Response Evaluation Criteria of Solid Tumor
(mRECIST) (i.e., the lesion can be accurately measured in
at least one dimension as 1 cm or more).
• The lesion is suitable for repeated measurement.
• The lesion shows intratumoral arterial enhancement on
contrast-enhanced CT or MRI.
ORR definition:
The objective response rate is defined as the percentage of all
treated patients who have complete response or partial response
of PTS100 treated tumors according to the assessment of target
lesion response by modified RECIST (mRECIST) criteria.
Patients without post-treatment tumor evaluation will be taken as
non-responder of objective response. Target lesion response is
assessed by radiological review and categorized as:
• Complete response (CR): the disappearance of any
intratumoral arterial enhancement in the target lesion.
• Partial response (PR): at least a 30% decrease in the sum of
diameters of viable (contrast enhancement in the arterial
phase) target lesions, taking as reference the baseline sum
of the diameters of target lesion.
• Stable disease (SD): any cases that do not qualify for either
partial response or progressive disease.
• Progressive disease (PD): an increase of at least 20% in the
sum of the diameters of viable (enhancing) target lesion,
taking as reference the smallest sum of the diameters of
viable (enhancing) target lesions recorded since the
treatment started.
Secondary Endpoints
1) Local disease control rate (LDCR) of treated target lesion at
the concluding visit. LDCR is defined as the percentage of
all treated patients who have complete response, partial
response, and stable disease of PTS100 treated tumors
according to the assessment of target lesion response by
modified RECIST (mRECIST) criteria.
2) Time to treated tumor progression (TTTTP) of pooled
treatment groups: time from first PTS100 administration to
treated tumor progression based on mRECIST, assessed at
concluding visit, then every 2 monthsfollow up with imaging
will be continued for 12 months. mRECIST will be used to
define local tumor progression. Local progression was
defined as 20% or more size increase of contrast enhanced
target lesion or new contrast enhanced lesion in target lesion.
3) Three-year overall survival (OS) of pooled treatment groups:
time from first IP administration to patient death or to the date
of 3 years after first IP administration, assessed every 2
months for 1 year and thereafter every 3 months for 2 more
years.
4) Time to tumor stage progression (TSP): defined as the time
from first IP administration to development of new
macrovascular invasion or appearance of new extrahepatic
spread in planning target volume assessed by imaging
methods during follow up.
5) Difference in ORR between group 1 and group 2 at
concluding visit.
6) Difference in LDCR between group 1 and group 2 at
concluding visit.
7) Difference in TTTTP between group 1 and group 2 at concluding
visit.
8) Safety: adverse events (AEs) as determined by CTCAE
version 4.0, serious adverse events (SAEs), vital sign
measurements, electrocardiograms (ECGs), physical
examinations, clinical laboratory tests, treatment
discontinuation rate and tolerability of the PTS100 injection
procedure (treatment-related AE incidence).
9) Quality of life score: assessed with FACT-Hep and EQ-5D
at screening visit, the concluding visit and first follow up
visit, before physician interview.
Objective Response Rate (ORR) at concluding visit:
Target lesion definition (the same as local/treated tumor in
this study):
• The lesion can be classified as a measurable lesion by
modified Response Evaluation Criteria of Solid Tumor
(mRECIST) (i.e., the lesion can be accurately measured in
at least one dimension as 1 cm or more).
• The lesion is suitable for repeated measurement.
• The lesion shows intratumoral arterial enhancement on
contrast-enhanced CT or MRI.
ORR definition:
The objective response rate is defined as the percentage of all
treated patients who have complete response or partial response
of PTS100 treated tumors according to the assessment of target
lesion response by modified RECIST (mRECIST) criteria.
Patients without post-treatment tumor evaluation will be taken as
non-responder of objective response. Target lesion response is
assessed by radiological review and categorized as:
• Complete response (CR): the disappearance of any
intratumoral arterial enhancement in the target lesion.
• Partial response (PR): at least a 30% decrease in the sum of
diameters of viable (contrast enhancement in the arterial
phase) target lesions, taking as reference the baseline sum
of the diameters of target lesion.
• Stable disease (SD): any cases that do not qualify for either
partial response or progressive disease.
• Progressive disease (PD): an increase of at least 20% in the
sum of the diameters of viable (enhancing) target lesion,
taking as reference the smallest sum of the diameters of
viable (enhancing) target lesions recorded since the
treatment started.
Secondary Endpoints
1) Local disease control rate (LDCR) of treated target lesion at
the concluding visit. LDCR is defined as the percentage of
all treated patients who have complete response, partial
response, and stable disease of PTS100 treated tumors
according to the assessment of target lesion response by
modified RECIST (mRECIST) criteria.
2) Time to treated tumor progression (TTTTP) of pooled
treatment groups: time from first PTS100 administration to
treated tumor progression based on mRECIST, assessed at
concluding visit, then every 2 monthsfollow up with imaging
will be continued for 12 months. mRECIST will be used to
define local tumor progression. Local progression was
defined as 20% or more size increase of contrast enhanced
target lesion or new contrast enhanced lesion in target lesion.
3) Three-year overall survival (OS) of pooled treatment groups:
time from first IP administration to patient death or to the date
of 3 years after first IP administration, assessed every 2
months for 1 year and thereafter every 3 months for 2 more
years.
4) Time to tumor stage progression (TSP): defined as the time
from first IP administration to development of new
macrovascular invasion or appearance of new extrahepatic
spread in planning target volume assessed by imaging
methods during follow up.
5) Difference in ORR between group 1 and group 2 at
concluding visit.
6) Difference in LDCR between group 1 and group 2 at
concluding visit.
7) Difference in TTTTP between group 1 and group 2 at concluding
visit.
8) Safety: adverse events (AEs) as determined by CTCAE
version 4.0, serious adverse events (SAEs), vital sign
measurements, electrocardiograms (ECGs), physical
examinations, clinical laboratory tests, treatment
discontinuation rate and tolerability of the PTS100 injection
procedure (treatment-related AE incidence).
9) Quality of life score: assessed with FACT-Hep and EQ-5D
at screening visit, the concluding visit and first follow up
visit, before physician interview.
Inclution Criteria
A patient is eligible for the study if all of the following apply:
1. Male or female, ≥ 20 years and ≤ 80 years of age.
2. Patients with clinically confirmed primary HCC following
American Association for the Study of Liver Diseases (AASLD,
Appendix 1) guidance:
a. Cyto-histological evidence
b. Coincident imaging evidence using computerized tomography
(CT) or magnetic resonance imaging (MRI)
3. Based on investigator discretion, patients who are ineffective
or unsuitable for resection, immediate liver transplantation, Trans
Arterial Chemoembolization (TACE), or current local ablative
treatment and meet all of the following conditions at study entry:
a. Barcelona Clinic Liver Cancer (BCLC) stage B.
b. Eastern Cooperative Oncology Group (ECOG) performance
status of 0 to 1.
c. Child Pugh score class A.
4. Patients with at least one measurable lesion with size ≥ 1 cm.
5. Patients with cumulative total treated tumor volume ≤ 600 cm3
.
6. Patients with adequate bone marrow, liver and renal function
within 28 days prior to study entry, as defined by the following:
a. Hemoglobin > 10.0 g/dl.
b. Absolute neutrophil count (ANC) > 1,500/mm3
.
c. Platelet count > 80k/mm3
correctable by component therapy.
d. Albumin ≥ 3 g/dl.
e. Total bilirubin < 2 mg/dL.
f. Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) < 5 x upper normal limit (UNL).
g. Blood urea nitrogen (BUN) and serum creatinine < 1.5 x UNL.
h. International normalized ratio (INR) < 1.5 or prothrombin time
(PT) < 15 seconds.
7. Patients with life expectancy > 3 months as judged by
investigator.
8. Patients who understand and comply to the study procedure
and be willing to provide a written informed consent form.
Note: Definition of TACE failure/refractoriness (LCSGJ)
(A) Intrahepatic lesion
(i) Two or more consecutive insufficient responses of the treated
tumor (viable lesion >50%) even after changing
the chemotherapeutic agents and/or reanalysis of the feeding
artery seen on response evaluation CT/MRI at 1–3 months after
having adequately performed selective TACE.
(ii) Two or more consecutive progressions in the liver (tumor
number increases as compared to tumor number before the
previous TACE procedure) even after having changed the
chemotherapeutic agents and/or reanalysis of the feeding artery
seen on response evaluation CT/MRI at 1–3 months after having
adequately performed selective TACE.
(B) Continuous elevation of tumor markers immediately after
TACE even though slight transient decrease is observed.
(C) Appearance of vascular invasion.
(D) Appearance of extrahepatic spread.
1. Male or female, ≥ 20 years and ≤ 80 years of age.
2. Patients with clinically confirmed primary HCC following
American Association for the Study of Liver Diseases (AASLD,
Appendix 1) guidance:
a. Cyto-histological evidence
b. Coincident imaging evidence using computerized tomography
(CT) or magnetic resonance imaging (MRI)
3. Based on investigator discretion, patients who are ineffective
or unsuitable for resection, immediate liver transplantation, Trans
Arterial Chemoembolization (TACE), or current local ablative
treatment and meet all of the following conditions at study entry:
a. Barcelona Clinic Liver Cancer (BCLC) stage B.
b. Eastern Cooperative Oncology Group (ECOG) performance
status of 0 to 1.
c. Child Pugh score class A.
4. Patients with at least one measurable lesion with size ≥ 1 cm.
5. Patients with cumulative total treated tumor volume ≤ 600 cm3
.
6. Patients with adequate bone marrow, liver and renal function
within 28 days prior to study entry, as defined by the following:
a. Hemoglobin > 10.0 g/dl.
b. Absolute neutrophil count (ANC) > 1,500/mm3
.
c. Platelet count > 80k/mm3
correctable by component therapy.
d. Albumin ≥ 3 g/dl.
e. Total bilirubin < 2 mg/dL.
f. Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) < 5 x upper normal limit (UNL).
g. Blood urea nitrogen (BUN) and serum creatinine < 1.5 x UNL.
h. International normalized ratio (INR) < 1.5 or prothrombin time
(PT) < 15 seconds.
7. Patients with life expectancy > 3 months as judged by
investigator.
8. Patients who understand and comply to the study procedure
and be willing to provide a written informed consent form.
Note: Definition of TACE failure/refractoriness (LCSGJ)
(A) Intrahepatic lesion
(i) Two or more consecutive insufficient responses of the treated
tumor (viable lesion >50%) even after changing
the chemotherapeutic agents and/or reanalysis of the feeding
artery seen on response evaluation CT/MRI at 1–3 months after
having adequately performed selective TACE.
(ii) Two or more consecutive progressions in the liver (tumor
number increases as compared to tumor number before the
previous TACE procedure) even after having changed the
chemotherapeutic agents and/or reanalysis of the feeding artery
seen on response evaluation CT/MRI at 1–3 months after having
adequately performed selective TACE.
(B) Continuous elevation of tumor markers immediately after
TACE even though slight transient decrease is observed.
(C) Appearance of vascular invasion.
(D) Appearance of extrahepatic spread.
Exclusion Criteria
Any patient meeting any of the exclusion criteria will be
excluded from study participation:
1. Infiltrative HCC or tumor burden ≥ 50% of liver parenchyma.
2. Presence of metastasis in biliary tract, brain or bone.
3. Systemic chemotherapy treatment for HCC within 12 weeks
prior to study entry.
4. Major surgery within 4 weeks prior to study entry (e.g.
thoracolaparotomy is not allowed, but noninvasive surgery,
e.g. biopsy, is allowed).
5. Use of any investigational drugs, biologics, or devices within
4 weeks prior to study entry or planned use during the course
of study.
6. Any other severe disease (e.g. active infection, uncontrolled
diabetes mellitus, severe heart dysfunction or angina, gastric
ulcer, active auto-immune disease) judged by the investigator
to limit subject participation in the study.
7. Female subjects who are pregnant or lactating. Women of
childbearing potential must have a negative urine pregnancy
test performed within seven days prior to the start of study
drug and agree to practice medically acceptable contraceptive
regimen from screening until at least 28 days after the study
treatment. Patients who are postmenopausal for at least 1 year
(> 12 months since the last menstrual cycle) or were surgically
sterilized do not require the pregnancy test.
8. Known or suspected allergy and/or hypersensitivity to any of
the ingredients of PTS100.
9. Any condition, judged by investigator, that shows subjects
are not suitable for participation.
excluded from study participation:
1. Infiltrative HCC or tumor burden ≥ 50% of liver parenchyma.
2. Presence of metastasis in biliary tract, brain or bone.
3. Systemic chemotherapy treatment for HCC within 12 weeks
prior to study entry.
4. Major surgery within 4 weeks prior to study entry (e.g.
thoracolaparotomy is not allowed, but noninvasive surgery,
e.g. biopsy, is allowed).
5. Use of any investigational drugs, biologics, or devices within
4 weeks prior to study entry or planned use during the course
of study.
6. Any other severe disease (e.g. active infection, uncontrolled
diabetes mellitus, severe heart dysfunction or angina, gastric
ulcer, active auto-immune disease) judged by the investigator
to limit subject participation in the study.
7. Female subjects who are pregnant or lactating. Women of
childbearing potential must have a negative urine pregnancy
test performed within seven days prior to the start of study
drug and agree to practice medically acceptable contraceptive
regimen from screening until at least 28 days after the study
treatment. Patients who are postmenopausal for at least 1 year
(> 12 months since the last menstrual cycle) or were surgically
sterilized do not require the pregnancy test.
8. Known or suspected allergy and/or hypersensitivity to any of
the ingredients of PTS100.
9. Any condition, judged by investigator, that shows subjects
are not suitable for participation.
The Estimated Number of Participants
-
Taiwan
33 participants
-
Global
NA participants
