Unresectable Intrahepatic CholangiocarcinomaPhase 2NCT02994251
A Trial of Systemic Chemotherapy in Combination With Conventional Transarterial Chemoembolization in Patients With Advanced Intra-Hepatic Cholangiocarcinoma
A Phase 2 study testing gemcitabine, Cisplatin and Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C in people with Unresectable Intrahepatic Cholangiocarcinoma, run by Yale University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Intrahepatic Cholangiocarcinoma
- What is being tested?
- gemcitabine, Cisplatin and Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jun 2017to 6 Nov 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Hemoglobin ≥ 9 g/dL
Show all 19Show fewer
- Absolute neutrophil count ≥ 1500/mm3
- Creatinine ≤ 2.0 g/dL
- AST and ALT ≤ 5 x ULN
- Albumin ≥ 2.4 mg/dL
- Total bilirubin ≤ 2.5 mg/dL
- Platelets ≥ 100,000/mm3
- For TACE procedures, subjects are allowed to have platelets ≥ 75,000/mm3.
- 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.
Who cannot join
- Prior or concurrent chemotherapy treatment for advanced ICC.
- History of allergic reactions attributed to compounds of similar chemical or biological composition to gemcitabine, cisplatin, doxorubicin, or mitomycin-C.
- Active treatment with CYP3A4 strong inhibitors or inducers.
- Recent surgical procedure within 21 days of study enrollment.
- Severe and/or uncontrolled co-morbid medical conditions including, but not limited to, active infection, viral hepatitis, congestive heart failure, cardiac arrhythmia, unstable angina pectoris, and psychiatric illness or social circumstance that would limit compliance with study requirements.
- Pregnancy during study duration.
Show all 17Show fewer
- Active immunosuppressive medications.
- Presence of grade 2 or higher hepatic encephalopathy.
- Complete occlusion of the entire portal venous system. Partial or branch portal vein occlusion allowed if without reversal of flow.
- Radiotherapy within 21 days from treatment with study interventions or medications.
- Current, recent (within 4 weeks of first infusion of this study), or planned participation in additional experimental drug.
- Unstable angina.
- New York Heart Association (NYHA) Grade II or greater congestive heart failure (Appendix C).
- History of myocardial infarction or CVA within 6 months prior to study enrollment.
- Clinically significant peripheral vascular disease.
- Inability to comply with study and/or follow-up procedures.
- Life expectancy of less than 12 weeks.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Trial of Systemic Chemotherapy (Gemcitabine and Cisplatin) in Combination With Conventional Transarterial Chemoembolization (cTACE) in Patients With Advanced Intra-Hepatic Cholangiocarcinoma (ICC)
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.
Read the detailed description
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.
- Being tested
- gemcitabine, Cisplatin, Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gemcitabineDrug
1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities
CisplatinDrug
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-CDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: gemcitabine; Drug: Cisplatin; Drug: Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (6)
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.
Measured: 18 months
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study start21 Jun 2017
- Primary completion6 Nov 2018
- Study completion6 Nov 2018
Why it stopped: Study terminated due to low enrollment making it unlikely to meet recruitment goals.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Unresectable Intrahepatic CholangiocarcinomaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Todd Schlachter, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02994251
- Sponsor's protocol ID
- 1603017367
- Status last verified
- Dec 2019
- First submitted
- 6 Dec 2016
- Last updated
- 30 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Systemic Chemotherapy (Gemcitabine and Cisplatin) in Combination With Conventional Transarterial Chemoembolization (cTACE) in Patients With Advanced Intra-Hepatic Cholangiocarcinoma (ICC)
- ClinicalTrials.gov ID
- NCT02994251
- Acronym / sponsor ID
- 1603017367
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to low enrollment making it unlikely to meet recruitment goals.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 21 Jun 2017 (actual)
- Primary completion
- 6 Nov 2018 (actual)
- Study completion
- 6 Nov 2018 (actual)
- First posted
- 15 Dec 2016 (estimated)
- Results
- Posted 30 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Drug: gemcitabine, Drug: Cisplatin, Drug: Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-CPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
Key exclusion criteria (17 listed)
- Prior or concurrent chemotherapy treatment for advanced ICC.
- History of allergic reactions attributed to compounds of similar chemical or biological composition to gemcitabine, cisplatin, doxorubicin, or mitomycin-C.
- Active treatment with CYP3A4 strong inhibitors or inducers.
- Recent surgical procedure within 21 days of study enrollment.
- Severe and/or uncontrolled co-morbid medical conditions including, but not limited to, active infection, viral hepatitis, congestive heart failure, cardiac arrhythmia, unstable angina pectoris, and psychiatric illness or social circumstance that would limit compliance with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gemcitabine1000 mg/m^2 of gemcitabine on Day 1 and 8, Dosages may be modified or delayed due to toxicities | Drug | All subjects |
| Cisplatin25 mg/m^2 on Day 1 and 8, Dosages may be modified or delayed due to toxicities | Drug | All subjects |
| Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-CIf 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. | Drug | All subjects |
Primary outcome
Progression-free Survival
Time frame: 12 months
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.
6 secondary outcomes
Overall Survival
Time frame: 18 months
Overall Time to Progression (TTP)
Time frame: up to 18 months
Time to Untreatable Progression (TTUP)
Time frame: 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.
Time frame: 18 months
Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Progression Free Survival
Time frame: 18 months
Correlation Between Changes in Dynamic Contrast-enhanced MRI of Liver Lesions and Overall Survival
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Unresectable Intrahepatic Cholangiocarcinoma
Not yet recruitingPhase 3
Intraarterial Therapies Plus Tislelizumab Plus Lenvatinib Versus Tislelizumab Plus Gemcitabine-Cisplatin in Unresectable Intrahepatic Cholangiocarcinoma
Intrahepatic Cholangiocarcinoma (Icc)
Active, not recruitingPhase 2
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
Metastatic Cholangiocarcinoma, Metastatic Hepatocellular Carcinoma
RecruitingPhase 2
Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extra- and Intrahepatic Cholangiocarcinoma
Extrahepatic Cholangiocarcinoma, Unresectable Perihilar or Ductal CCA
RecruitingPhase 2
Gemcitabine and Oxaliplatin Chemotherapy With or Without a Floxuridine and Dexamethasone Pump in People With Cholangiocarcinoma That Cannot Be Removed With Surgery
Intrahepatic Cholangiocarcinoma
Active, not recruitingPhase 2
Study of Chemotherapy, With or Without Binimetinib in Advanced Biliary Tract Cancers in 2nd Line Setting (A ComboMATCH Treatment Trial)
Advanced Biliary Tract Carcinoma, Advanced Gallbladder Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Todd Schlachter principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing gemcitabine, Cisplatin and Conventional TACE (transarterial chemoembolization) with Doxorubicin/Mitomycin-C in people with Unresectable Intrahepatic Cholangiocarcinoma, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2019.