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Study terminated due to low enrollment making it unlikely to meet recruitment goals.
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The study will be a single-center, single-arm, Phase II study of gemcitabine and cisplatin in combination with conventional trans-arterial chemoembolization therapy in adult patients with advanced ICC. 25 patients will be enrolled over the course of 2 years, with an additional 1.5 years for patient follow-up.
Eligible patients enrolled on study will receive a chemotherapy regimen of gemcitabine and cisplatin administered intravenously on Days 1 and 8 of a 21-day cycle. After every 2 cycles of systemic chemotherapy, patients will receive contrast-enhanced MRI to assess liver disease; conventional trans-arterial chemoembolization (TACE) will be performed as indicated based on this assessment. Patients will receive a maximum of 8 cycles of the gemcitabine/cisplatin combination. Up to 3 TACE treatments may be delivered in this same time frame, with the first TACE taking place after 2 cycles of systemic chemotherapy. Following the treatment period, patients will continue clinical follow-up at 3 month intervals until study exit at 18 months post the start of treatment.
It is hypothesized that the addition of conventional transarterial chemoembolization to standard chemotherapy will result in an improvement in PFS in patients with advanced, unresectable ICC, including patients with extra-hepatic disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All subjects | Experimental | Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| gemcitabine | Drug | 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities |
|
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival | The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit. | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Evaluation of overall survival (OS) of adult patients with advanced ICC treated with gemcitabine and cisplatin in combination with conventional TACE. Overall survival is the time from enrollment on study until death of the patient from any cause. | 18 months |
| Overall Time to Progression (TTP) |
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Inclusion Criteria:
Patient is at least 18 years of age.
Patient has advanced, unresectable intrahepatic cholangiocarcinoma (ICC). Advanced, unresectable ICC is defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection.
Eligible for conventional TACE as defined by local treatment guidelines.
Child-Pugh class of A to B7.
Adequate end-organ and bone marrow function as manifested as:
Disease is liver-dominant with >70% of measurable disease burden within the hepatic parenchyma.
No prior surgery or chemotherapy for ICC.
ECOG performance status of 0-1.
No other active malignancy within 2 years.
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study.
Ability to understand and willingness to sign a written informed consent document.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Todd Schlachter | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Smilow Cancer Center | New Haven | Connecticut | 06510 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Subjects | Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection. gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 19, 2018 |
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| Cisplatin | Drug | 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities |
|
| Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C | Drug | If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand. |
|
Overall TTP is the time from enrollment on study until radiographic evidence of overall disease progression. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy. |
| up to 18 months |
| Time to Untreatable Progression (TTUP) | TTUP in liver lesions is measured from the time of initiation on cTACE therapy until radiographic evidence of disease progression in targeted lesions. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy. | up to 18 months |
| Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. | To evaluate the toxicities of the gemcitabine and cisplatin regimen in combination with cTACE therapy in adult patients with advanced ICC. Safety will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | 18 months |
| Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival | early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term PFS or OS, specifically as they relate to lesions targeted with cTACE therapy | 18 months |
| Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival | early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term OS, specifically as they relate to lesions targeted with cTACE therapy | 18 months |
| COMPLETED |
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| NOT COMPLETED |
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Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject.
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| ID | Title | Description |
|---|---|---|
| BG000 | All Subjects | Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection. gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
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| Age, Continuous | |||||||||||||||||||||||||||||||
| Sex: Female, Male |
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| Race (NIH/OMB) |
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| Region of Enrollment | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Progression-free Survival | The primary objective of this study is to evaluate the 12-month progression-free survival (PFS) rate in adult patients with intrahepatic cholangiocarcinoma (ICC) after treatment with gemcitabine and cisplatin in combination with conventional TACE. This is the percentage of patients alive and free of progression at 12-months from enrollment on study. Radiographic assessment of disease burden will be evaluated by mRECIST and qEASL using an MRI scan obtained at the IR clinic visit. | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | 12 months |
|
| |||||||||||||||||||
| Secondary | Overall Survival | Evaluation of overall survival (OS) of adult patients with advanced ICC treated with gemcitabine and cisplatin in combination with conventional TACE. Overall survival is the time from enrollment on study until death of the patient from any cause. | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | 18 months |
| ||||||||||||||||||||
| Secondary | Overall Time to Progression (TTP) | Overall TTP is the time from enrollment on study until radiographic evidence of overall disease progression. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy. | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | up to 18 months |
|
| |||||||||||||||||||
| Secondary | Time to Untreatable Progression (TTUP) | TTUP in liver lesions is measured from the time of initiation on cTACE therapy until radiographic evidence of disease progression in targeted lesions. Radiographic assessment will be evaluated by mRECIST using MRI every 2 cycles after intra-arterial therapy. | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | up to 18 months |
| ||||||||||||||||||||
| Secondary | Toxicities of the Gemcitabine and Cisplatin Regimen in Combination With cTACE Therapy Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. | To evaluate the toxicities of the gemcitabine and cisplatin regimen in combination with cTACE therapy in adult patients with advanced ICC. Safety will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | 18 months |
| ||||||||||||||||||||
| Secondary | Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival | early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term PFS or OS, specifically as they relate to lesions targeted with cTACE therapy | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | 18 months |
| ||||||||||||||||||||
| Secondary | Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival | early changes in dynamic contrast-enhanced MRI (DCE-MRI) will correlate with long term OS, specifically as they relate to lesions targeted with cTACE therapy | Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed. | Posted | 18 months |
|
|
Adverse events collected at baseline until patient exit at 18 months post start of therapy.
Confidentiality is a concern as the study was terminated after 1 patient was enrolled, thus any reported data would indicate PHI for this subject. To prevent this, it was advised to enter 0 as the number of participants analyzed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Subjects | Patients must have advanced, unresectable intrahepatic cholangiocarcinoma (ICC) defined as biopsy-confirmed adenocarcinoma in the liver, with an immunohistochemical profile consistent with a pancreatico-biliary primary, not involving the common bile duct or bifurcation, and not amenable to surgical resection. gemcitabine: 1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities Cisplatin: 25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C: If conventional transarterial chemoembolization (TACE) is warranted based on MRI assessment and the patient meets all the eligibility criteria for TACE therapy, then cTACE will be scheduled to take place during Week 3 of that cycle. Patients will always receive the first cTACE for study; follow-up cTACE will occur on demand. | 0 | 0 | 0 | 0 | 0 | 0 |
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Trial was terminated early due to low enrollment, leading to endpoints not being achievable.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Todd Schlachter | Yale University | 203-785-5885 | todd.schlachter@yale.edu |
| Dec 6, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| D002945 | Cisplatin |
| D016685 | Mitomycin |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D008937 | Mitomycins |
| D045563 | Indolequinones |
| D011809 | Quinones |
| D009930 | Organic Chemicals |
| D001389 | Azirines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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