Clinical Trials List
Protocol NumberS4-13-001
NCT Number(ClinicalTrials.gov Identfier)NCT02128282
2016-01-01 - 2021-05-31
Phase I/II
Recruiting6
ICD-10C22.0
Liver cell carcinoma
ICD-10C22.1
Intrahepatic bile duct carcinoma
A Phase I/II Study of CX-4945 in Combination with Gemcitabine plus Cisplatin in the Frontline Treatment of Patients with Cholangiocarcinoma
-
Trial Applicant
Syneos Health
-
Sponsor
Senhwa Biosciences Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Chang-Fang Chiu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yan-Shen Shan Division of General Surgery
- Shang-Hung Chen Division of Hematology & Oncology
- Nai-Jung Chiang Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
- 趙盈瑞 Division of General Surgery
- Li-Tzong Chen Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
8 Recruiting
Audit
None
Co-Principal Investigator
- Tai-Jan Chiu Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
陳仁熙
Co-Principal Investigator
- Hung-Chih Hsu Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
2 Recruiting
Audit
None
Co-Principal Investigator
- Ying-Chun Shen Division of Hematology & Oncology
- JHE-CYUAN GUO 未分科
- 林育麟 Division of Hematology & Oncology
- 呂理駿 未分科
- Ann-Lii Cheng Division of Hematology & Oncology
- SHIH-HUNG YANG Division of Hematology & Oncology
- Chih-Hung Hsu Division of Hematology & Oncology
- YU-YUN SHAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Cholangiocarcinoma
Objectives
This study considers the safety and tolerability of increasing doses of CX-4945 in combination with gemcitabine plus cisplatin to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D), followed by a randomized study that compares antitumor activity in cholangiocarcinoma patients receiving the standard of care gemcitabine plus cisplatin versus CX-4945 at the combination RP2D with gemcitabine plus cisplatin.
Test Drug
CX-4945
Active Ingredient
CX-4945
Dosage Form
capsule
Dosage
200mg
Endpoints
Primary Outcome Measures :
1. Maximum Tolerated Dose (MTD) of CX-4945 when used in combination with gemcitabine plus cisplatin. (Phase 1) [ Time Frame: Cycle 1, 1 Full cycle up to twenty-one (21) days ]
The Maximum Tolerated Dose of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is escalated in cohorts of three patients in combination with standard gemcitabine plus cisplatin.
2. Comparison of the Progression-free survival (PFS) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 (Phase 2) [ Time Frame: From date of randomization to date of progression or death from any cause up to 52 weeks. ]
Tumor measurements will be compared to baseline every six weeks, and the PFS will be determined using RECIST v. 1.1.
3. Recommended Phase II dose (RP2D) and schedule of CX-4945 in combination with gemcitabine plus cisplatin (Phase I) [ Time Frame: Cycle 1, 1 Full cycle up to twenty-one (21) days ]
The recommended Phase II dose and schedule of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is administered 1000mg BID in 10-day continuous or 21-day continuous cohorts in combination with standard gemcitabine plus cisplatin.
Secondary Outcome Measures :
1. Comparison of the Overall Response Rate (ORR) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 [ Time Frame: From date of randomization to date of progression or death from any cause up to 52 weeks. ]
Tumor measurements will be compared to baseline, and the ORR will be determined using RECIST v. 1.1
2. Comparison of the number of patient who transition to surgical resection [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]
The number of patients in the chemotherapy arm versus CX-4945 plus chemotherapy arm who transition to surgical resection will be compared.
3. Comparison of the Overall Survival (OS) between the test and the control arms [ Time Frame: From date of randomization to date of death from any cause up to 52 weeks. ]
Time to event is observed during treatment and followed up every 3 months after patient withdraw from treatment.
1. Maximum Tolerated Dose (MTD) of CX-4945 when used in combination with gemcitabine plus cisplatin. (Phase 1) [ Time Frame: Cycle 1, 1 Full cycle up to twenty-one (21) days ]
The Maximum Tolerated Dose of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is escalated in cohorts of three patients in combination with standard gemcitabine plus cisplatin.
2. Comparison of the Progression-free survival (PFS) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 (Phase 2) [ Time Frame: From date of randomization to date of progression or death from any cause up to 52 weeks. ]
Tumor measurements will be compared to baseline every six weeks, and the PFS will be determined using RECIST v. 1.1.
3. Recommended Phase II dose (RP2D) and schedule of CX-4945 in combination with gemcitabine plus cisplatin (Phase I) [ Time Frame: Cycle 1, 1 Full cycle up to twenty-one (21) days ]
The recommended Phase II dose and schedule of CX-4945 will be determined from safety observations during the first cycle, as the CX-4945 dose is administered 1000mg BID in 10-day continuous or 21-day continuous cohorts in combination with standard gemcitabine plus cisplatin.
Secondary Outcome Measures :
1. Comparison of the Overall Response Rate (ORR) between the test and the control arms using Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 [ Time Frame: From date of randomization to date of progression or death from any cause up to 52 weeks. ]
Tumor measurements will be compared to baseline, and the ORR will be determined using RECIST v. 1.1
2. Comparison of the number of patient who transition to surgical resection [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ]
The number of patients in the chemotherapy arm versus CX-4945 plus chemotherapy arm who transition to surgical resection will be compared.
3. Comparison of the Overall Survival (OS) between the test and the control arms [ Time Frame: From date of randomization to date of death from any cause up to 52 weeks. ]
Time to event is observed during treatment and followed up every 3 months after patient withdraw from treatment.
Inclution Criteria
Patients meeting all of the following criteria will be
considered for admission to the study:
1. Signed, written IRB-approved informed consent.
2. Presence of an unresectable hepatobiliary mass consistent
with cholangiocarcinoma, as evidenced by histology or
cytology (augmented by fluorescence in situ hybridization
(FISH) where appropriate), for which treatment with
gemcitabine plus cisplatin is intended. Intrahepatic and
extrahepatic cholangiocarcinoma patients may be enrolled.
Cancers clearly originating from the gall bladder or
ampulla of Vater are excluded.
3. At least 18 years of age.
4. For patients enrolled in the Dose Escalation Phase and the
Exploratory Cohorts, one or more tumors measurable on
radiograph or CT scan, or evaluable disease defined as
non-measurable lesions per RECIST v.1.1 (e.g., malignant
ascites). All patients enrolled to the Expansion Cohort,
and the Randomized Study Phase must have measurable
disease.
5. Laboratory data as specified below:
• Hematology: ANC >1,500 cells/mm3
, platelet
count >100,000 cells/mm3 and hemoglobin > 9
g/dL
• Hepatic: bilirubin <1.5 X ULN; alkaline
phosphatase (ALP), alanine aminotransferase
(ALT) or aspartate aminotransferase (AST) < 5.0X ULN
• Renal: serum creatinine within normal limits
(WNL), defined as ±25% of the institution’s stated
reference range, or a calculated creatinine
clearance >45 mL/min for patients with abnormal,
increased, creatinine levels (Cockcroft-Gault
formula; Appendix I).
• Coagulation: INR < 1.5 times normal, aPTT < 1.5
times normal. Patients receiving therapeutic doses
of anticoagulant therapy may be considered
eligible for the trial if INR and aPTT are within the
acceptable therapeutic limits for the institution.
6. A negative pregnancy test (if female of childbearing
potential).
7. Estimated life expectancy of at least 3 months.
8. ECOG Performance Status 0-1.
9. For men and women of child-producing potential, use of
effective contraceptive methods during the study. NOTE:
All women of child-bearing potential and men must agree
to use adequate contraception (hormonal or barrier method
of birth control; or abstinence) prior to study entry and for
the duration of study participation. Should a man father a
child, or a woman become pregnant or suspect she is
pregnant while participating in this study, he or she should
inform the treating physician immediately.
10. Ability to understand the requirements of the study,
provide written informed consent and authorization of use
and disclosure of protected health information, and
agreement to abide by the study restrictions and to return
to the clinic for the required assessments.
Additional criteria for Randomized Study Phase:
11. Patients must have a formalin-fixed paraffin-embedded
(FFPE) tissue block (from primary or metastatic tumor)
available and must have provided informed consent for the
release of the FFPE tissue block for subgroup analysis at
the end of the study. If an archival tumor tissue sample is
not available, a fresh tumor biopsy will be performed.
considered for admission to the study:
1. Signed, written IRB-approved informed consent.
2. Presence of an unresectable hepatobiliary mass consistent
with cholangiocarcinoma, as evidenced by histology or
cytology (augmented by fluorescence in situ hybridization
(FISH) where appropriate), for which treatment with
gemcitabine plus cisplatin is intended. Intrahepatic and
extrahepatic cholangiocarcinoma patients may be enrolled.
Cancers clearly originating from the gall bladder or
ampulla of Vater are excluded.
3. At least 18 years of age.
4. For patients enrolled in the Dose Escalation Phase and the
Exploratory Cohorts, one or more tumors measurable on
radiograph or CT scan, or evaluable disease defined as
non-measurable lesions per RECIST v.1.1 (e.g., malignant
ascites). All patients enrolled to the Expansion Cohort,
and the Randomized Study Phase must have measurable
disease.
5. Laboratory data as specified below:
• Hematology: ANC >1,500 cells/mm3
, platelet
count >100,000 cells/mm3 and hemoglobin > 9
g/dL
• Hepatic: bilirubin <1.5 X ULN; alkaline
phosphatase (ALP), alanine aminotransferase
(ALT) or aspartate aminotransferase (AST) < 5.0X ULN
• Renal: serum creatinine within normal limits
(WNL), defined as ±25% of the institution’s stated
reference range, or a calculated creatinine
clearance >45 mL/min for patients with abnormal,
increased, creatinine levels (Cockcroft-Gault
formula; Appendix I).
• Coagulation: INR < 1.5 times normal, aPTT < 1.5
times normal. Patients receiving therapeutic doses
of anticoagulant therapy may be considered
eligible for the trial if INR and aPTT are within the
acceptable therapeutic limits for the institution.
6. A negative pregnancy test (if female of childbearing
potential).
7. Estimated life expectancy of at least 3 months.
8. ECOG Performance Status 0-1.
9. For men and women of child-producing potential, use of
effective contraceptive methods during the study. NOTE:
All women of child-bearing potential and men must agree
to use adequate contraception (hormonal or barrier method
of birth control; or abstinence) prior to study entry and for
the duration of study participation. Should a man father a
child, or a woman become pregnant or suspect she is
pregnant while participating in this study, he or she should
inform the treating physician immediately.
10. Ability to understand the requirements of the study,
provide written informed consent and authorization of use
and disclosure of protected health information, and
agreement to abide by the study restrictions and to return
to the clinic for the required assessments.
Additional criteria for Randomized Study Phase:
11. Patients must have a formalin-fixed paraffin-embedded
(FFPE) tissue block (from primary or metastatic tumor)
available and must have provided informed consent for the
release of the FFPE tissue block for subgroup analysis at
the end of the study. If an archival tumor tissue sample is
not available, a fresh tumor biopsy will be performed.
Exclusion Criteria
1. Pregnant or nursing women.
2. A history of prior systemic treatment with gemcitabine or
cisplatin. At least six months must have elapsed if
gemcitabine or cisplatin was administered in an adjuvant
treatment setting. Patients enrolled in the Expansion
Cohort, Exploratory Cohorts, and the Randomized Study
Phase must not have received prior systemic
chemotherapies, including chemoradiation therapy.
3. Seizure disorders requiring anticonvulsant therapy.
4. Known brain metastases (unless previously treated and
well controlled for a period of ≥ 3 months).
5. Major surgery other than diagnostic surgery, within 4
weeks prior to the first dose of test drug, minor surgery
including diagnostic surgery within 2 weeks (14 days)
excluding central IV port placements and needle
aspirate/core biopsies. Radio frequency ablation or
transcatheter arterial chemoembolization within 6 weeks
prior to the first dose of test drug.
6. Treatment with radiation therapy or surgery within one
month prior to study entry.
7. Treatment with chemotherapy or investigational drugs
within 21 days prior to the screening visit. Acute
toxicities from prior therapy must have resolved to Grade
≤ 1 above baseline.
8. Patients with a history of another malignancy within 3
years of the baseline visit. (Patients with cutaneous
carcinomas or in-situ carcinomas will be considered for
study entry on a case-by-case basis).
9. Concurrent severe or uncontrolled medical disease (i.e.,
systemic infection, diabetes, hypertension, coronary artery
disease, congestive heart failure).
10. Active symptomatic fungal, bacterial and/or viral infection
including active HIV or viral (A, B or C) hepatitis.
11. Difficulty with swallowing or an active malabsorption
syndrome.
12. Chronic diarrhea (excess of 2-3 stools/day above normal
frequency).
13. Gastrointestinal diseases including ulcerative colitis,
Crohn’s disease, or hemorrhagic coloproctitis.
14. History of gastric or small bowel surgery involving any
extent of gastric or small bowel resection.
15. Clinically significant bleeding event within the last 3
months, unrelated to trauma, or underlying condition that
would be expected to result in a bleeding diathesis.
16. Patients who have exhibited allergic reactions to a similar
structural compound or to a formulation component of
CX-4945.
17. Concomitant use either of warfarin and/or HMG-CoA
reductase inhibitors (statins).
2. A history of prior systemic treatment with gemcitabine or
cisplatin. At least six months must have elapsed if
gemcitabine or cisplatin was administered in an adjuvant
treatment setting. Patients enrolled in the Expansion
Cohort, Exploratory Cohorts, and the Randomized Study
Phase must not have received prior systemic
chemotherapies, including chemoradiation therapy.
3. Seizure disorders requiring anticonvulsant therapy.
4. Known brain metastases (unless previously treated and
well controlled for a period of ≥ 3 months).
5. Major surgery other than diagnostic surgery, within 4
weeks prior to the first dose of test drug, minor surgery
including diagnostic surgery within 2 weeks (14 days)
excluding central IV port placements and needle
aspirate/core biopsies. Radio frequency ablation or
transcatheter arterial chemoembolization within 6 weeks
prior to the first dose of test drug.
6. Treatment with radiation therapy or surgery within one
month prior to study entry.
7. Treatment with chemotherapy or investigational drugs
within 21 days prior to the screening visit. Acute
toxicities from prior therapy must have resolved to Grade
≤ 1 above baseline.
8. Patients with a history of another malignancy within 3
years of the baseline visit. (Patients with cutaneous
carcinomas or in-situ carcinomas will be considered for
study entry on a case-by-case basis).
9. Concurrent severe or uncontrolled medical disease (i.e.,
systemic infection, diabetes, hypertension, coronary artery
disease, congestive heart failure).
10. Active symptomatic fungal, bacterial and/or viral infection
including active HIV or viral (A, B or C) hepatitis.
11. Difficulty with swallowing or an active malabsorption
syndrome.
12. Chronic diarrhea (excess of 2-3 stools/day above normal
frequency).
13. Gastrointestinal diseases including ulcerative colitis,
Crohn’s disease, or hemorrhagic coloproctitis.
14. History of gastric or small bowel surgery involving any
extent of gastric or small bowel resection.
15. Clinically significant bleeding event within the last 3
months, unrelated to trauma, or underlying condition that
would be expected to result in a bleeding diathesis.
16. Patients who have exhibited allergic reactions to a similar
structural compound or to a formulation component of
CX-4945.
17. Concomitant use either of warfarin and/or HMG-CoA
reductase inhibitors (statins).
The Estimated Number of Participants
-
Taiwan
70 participants
-
Global
211 participants
