PTS100(hepatocellular carcinoma)-Clinical Trials
Clinical Trials List
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
Condition/Disease
Hepatocellular Carcinoma (HCC)
Protocol Number: GW-020202
NCT Number (ClinicalTrials.gov Identifier): NCT03447951
Recruiting 3 Sites : 2017-01-01 - 2028-05-31. Phase II
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 the 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.
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 a 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-responders 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 the 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 a 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 the concluding visit, then every 2 months follow up with imaging will be continued for 12 months. mRECIST will be used to define local tumor progression. Local progression was defined as a 20% or more size increase of a contrast-enhanced target lesion or a new contrast-enhanced lesion in a 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 the screening visit, the concluding visit, and the first follow-up visit, before the 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, transarterial 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 a 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 the investigator.
8. Patients who understand and comply with the study procedure and are 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, transarterial 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 a 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 the investigator.
8. Patients who understand and comply with the study procedure and are 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 the 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., thoracoparotomy 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 the investigator, that shows subjects are not suitable for participation.
1. Infiltrative HCC or tumor burden ≥ 50% of liver parenchyma.
2. Presence of metastasis in the 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., thoracoparotomy 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 the investigator, that shows subjects are not suitable for participation.
The Estimated Number of Participants
Taiwan
33 participants
Global
NA participants
Clinical Trial Information System:
https://reurl.cc/aeNGOY
https://reurl.cc/W0X1lZ
https://reurl.cc/7K3pOy
