Intrahepatic Cholangiocarcinoma RecurrentPhase 2NCT04523402
Neoadjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma With High Predict Risk of Lymph Node Metastasis
A Phase 2 study testing Neoadjuvant chemotherapy in people with Intrahepatic Cholangiocarcinoma Recurrent, run by Eastern Hepatobiliary Surgery Hospital.
Trial summary
A randomized controlled, open label, phase II clinical trial is designed to target patients with resectable intrahepatic cholangiocarcinoma (ICC) with high risk of lymph node metastasis as evaluated by our previously established radiomics model, which has low postoperative recurrence-free survival. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Intrahepatic Cholangiocarcinoma Recurrent
- What is being tested?
- Neoadjuvant chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- 31 Dec 2020to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sign written informed consent;
- Male or female patients aged 18-70;
- Eastern Cooperative Oncology Group (ECOG) score 0 points, Child-Pugh rating A;
- Clinically diagnosed as ICC as a potential entry, the neochemotherapy plus liver resection group must be histopathologically diagnosed as ICC before chemotherapy, and the liver resection alone group must be pathologically confirmed as intrahepatic cholangiocarcinoma after surgery;
- Resectable ICC patients with high risk of LN metastasis (Probability of LN metastasis ≥50% as evaluated by radiomics model);
- The subject has at least 1 measurable liver disease (according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1);
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- For women who are not breastfeeding or pregnant, use contraception during treatment or 3 months after the end of treatment.
- The functional indicators of important organs meet the following requirements:
- 1) Neutrophils≥1.5109/L; platelets≥90109/L; hemoglobin≥9g/dl; serum albumin≥3.5g/dl; 2) Coagulation function: International standardization (prothrombin time) ratio (INR) <1.2; 3) Thyroxine (T3 and T4) do not exceed the normal upper and lower limits by 2 times; 4) Bilirubin ≤ 1.5 times the upper limit of normal; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal; 5) Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥ 60ml/min;
Who cannot join
- Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-biliary cell carcinoma malignant tumor components;
- Patients who have recurrent ICC after surgery, or have chemotherapy in the past;
- Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
- Active tuberculosis infection. Patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, no formal anti-tuberculosis treatment or tuberculosis is still active;
- Suffer from active, known or suspected autoimmune diseases. Subjects with hypothyroidism who only need hormone replacement therapy and skin diseases without systemic therapy can be selected;
- Past interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy;
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- Long-term use of systemic hormones (dose equivalent to >10mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects using inhaled or topical corticosteroids can be selected;
- Active infections that require systemic treatment;
- Human immunodeficiency virus (human immunodeficiency virus [HIV], HIV1/2 antibody) positive;
- A history of psychotropic drug abuse, alcohol or drug abuse;
- Significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment;
- Suspected of being allergic to study drugs;
- Suffer from hypertension, and cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
- After antiviral therapy, hepatitis B virus (HBV)-DNA>104 copies/ml, hepatitis C virus (HCV)-RNA>1000;
- Accompanied by ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc. Combined with insufficiency of other organs, it is expected that they cannot accept general anesthesia or hepatectomy;
- Other factors judged by the investigator that may affect the safety of the subject or the compliance of the trial. Such as serious illnesses (including mental illness) that require combined treatment, serious laboratory abnormalities, other family or social factors, or participating in other clinical trials.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Oxaliplatin and Gemcitabine (GEMOX) Neoadjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma With High Risk of Lymph Node Metastasis as Preoperatively Evaluated by a Radiomics Model
A randomized controlled, open label, phase II clinical trial is designed to target patients with resectable intrahepatic cholangiocarcinoma (ICC) with high risk of lymph node metastasis as evaluated by our previously established radiomics model, which has low postoperative recurrence-free survival. In this study, we aim to compare the prognosis of ICC patients who undergo liver resection (LR) following preoperative oxaliplatin and gemcitabine (GEMOX) neoadjuvant therapy (experimental arm) versus LR alone (control arm).
Read the detailed description
Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer, and its incidence and mortality have been rising worldwide over the past two decades. Liver resection (LR) remains the only potentially curative treatment for ICC. However, the long-term outcome after LR is still dismal, and the 5-year survival after curative-intent resection was up to 35%. Lymph node (LN) metastasis is found in about 40% of ICC patients and is known to be one of the most important adverse prognostic factors. Considering such circumstances, it is crucial to determine the validity of routine LN dissection for ICC during LR, but there is so far no definitive evidence about the use of this surgical procedure. Preoperative individualized LN status assessment is beneficial for clinical decision of LN dissection and stratifying patients who may benefit from preoperative neoadjuvant therapy. The conventional and qualitative radiological characteristics in abdominal computerized tomography (CT) exhibited limited accuracy for preoperative assessment of LN status. Radiomics, a novel approach in medical image analysis, involves high-throughput extraction of quantitative image features and then associates these features with clinical concerns. The radiomic approach has been employed into preoperative diagnosis and prediction of prognosis. We have proposed a nomogram, incorporating conventional clinico-radiological characteristics and novel radiomic features in CT scan, provided accurate LN metastasis prediction in ICC patients and may aid the treatment decision making.
Neoadjuvant therapy refers to some treatments taken before surgery for newly treated tumor patients who have not found distant metastasis, including chemotherapy, radiotherapy, targeted therapy, etc., to reduce tumors, reduce tumor stages, and reduce postoperative recurrence rate, prolonging survival time. As suggested by the results from previous studies, neoadjuvant chemotherapy with oxaliplatin plus gemcitabine for locally advanced ICC may be an effective downstaging option, facilitating secondary resectability in patients with initially unresectable disease (53%, 39 in 74 patients received secondary resection). In addition, for selected patients with locally advanced ICC who showed pre-transplant disease stability on neoadjuvant chemotherapy could obtain 50% 5-year recurrence-free survival and 83.3% 5-year overall survival.
These evidences suggest that neoadjuvant chemotherapy with GEMOX regimen may be an ideal modality for patients with resectable ICC with high possibility of LN metastasis to reduce potential risk of recurrence, which is worth more investigation.
- Being tested
- Neoadjuvant chemotherapy
- Keywords
- Intrahepatic Cholangiocarcinoma; Neoadjuvant chemotherapy
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant chemotherapyDrug
Also called Preoperative chemotherapy
Neoadjuvant chemotherapy with GEMOX regimen before liver resection
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant chemotherapy following liver section | Experimental | 1. GEMOX chemotherapy:
1. It is performed within one week after the identification of ICC;
2. Day1 Oxaliplatin 85mg/m2 + gemcitabine 1g/m2, Day 8 gemcitabine 1g/m2;
3. Three weeks is a course of treatment;
4. A total of 3 courses.
2. Liver resection: It is performed 1 month after chemotherapy Receives: Drug: Neoadjuvant chemotherapy |
| Liver resection | No intervention | Liver resection: It is performed within one week after the identification of ICC. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival
The time period from randomization to the occurrence of the following events: disease progression prevents liver resection; local or distant recurrence; second primary tumor; death due to various causes.
Measured: 24 months
Secondary outcomes (3)
Overall survival
The time period from the randomization of the patient to the death event due to any reason.
Measured: 36 months
Objective response rate
The proportion of patients whose tumor volume has decreased to a predetermined value.
Measured: 4 months
Adverse events
The severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard the severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard the severity of adverse events will be evaluated according to the NCI CTCAE 5.0 standard.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start31 Dec 2020 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intrahepatic Cholangiocarcinoma RecurrentStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eastern Hepatobiliary Surgery Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shen Feng, Eastern Hepatobiliary Surgery Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04523402
- Sponsor's protocol ID
- EHBHKY2020-K-027
- Status last verified
- Aug 2020
- First submitted
- 19 Aug 2020
- Last updated
- 21 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oxaliplatin and Gemcitabine (GEMOX) Neoadjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma With High Risk of Lymph Node Metastasis as Preoperatively Evaluated by a Radiomics Model
- ClinicalTrials.gov ID
- NCT04523402
- Acronym / sponsor ID
- EHBHKY2020-K-027
- Keywords
- Intrahepatic Cholangiocarcinoma; Neoadjuvant chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Eastern Hepatobiliary Surgery HospitalUniversity, hospital or other
- Study start
- 31 Dec 2020 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 21 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized controlled, open label, phase II clinical trial is designed to target patients with resectable intrahepatic cholangiocarcinoma (ICC) with high risk of lymph node metastasis as evaluated by our previously established radiomics model, which has low postoperative recurrence-free survival. In this study, we aim to compare the prognosis of ICC patients who undergo liver resection (LR) following preoperative oxaliplatin and gemcitabine (GEMOX) neoadjuvant therapy (experimental arm) versus LR alone (control arm).
Detailed description
Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer, and its incidence and mortality have been rising worldwide over the past two decades. Liver resection (LR) remains the only potentially curative treatment for ICC. However, the long-term outcome after LR is still dismal, and the 5-year survival after curative-intent resection was up to 35%. Lymph node (LN) metastasis is found in about 40% of ICC patients and is known to be one of the most important adverse prognostic factors. Considering such circumstances, it is crucial to determine the validity of routine LN dissection for ICC during LR, but there is so far no definitive evidence about the use of this surgical procedure. Preoperative individualized LN status assessment is beneficial for clinical decision of LN dissection and stratifying patients who may benefit from preoperative neoadjuvant therapy. The conventional and qualitative radiological characteristics in abdominal computerized tomography (CT) exhibited limited accuracy for preoperative assessment of LN status. Radiomics, a novel approach in medical image analysis, involves high-throughput extraction of quantitative image features and then associates these features with clinical concerns. The radiomic approach has been employed into preoperative diagnosis and prediction of prognosis. We have proposed a nomogram, incorporating conventional clinico-radiological characteristics and novel radiomic features in CT scan, provided accurate LN metastasis prediction in ICC patients and may aid the treatment decision making.
Neoadjuvant therapy refers to some treatments taken before surgery for newly treated tumor patients who have not found distant metastasis, including chemotherapy, radiotherapy, targeted therapy, etc., to reduce tumors, reduce tumor stages, and reduce postoperative recurrence rate, prolonging survival time. As suggested by the results from previous studies, neoadjuvant chemotherapy with oxaliplatin plus gemcitabine for locally advanced ICC may be an effective downstaging option, facilitating secondary resectability in patients with initially unresectable disease (53%, 39 in 74 patients received secondary resection). In addition, for selected patients with locally advanced ICC who showed pre-transplant disease stability on neoadjuvant chemotherapy could obtain 50% 5-year recurrence-free survival and 83.3% 5-year overall survival.
These evidences suggest that neoadjuvant chemotherapy with GEMOX regimen may be an ideal modality for patients with resectable ICC with high possibility of LN metastasis to reduce potential risk of recurrence, which is worth more investigation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant chemotherapy following liver section | Experimental | Drug: Neoadjuvant chemotherapy1. GEMOX chemotherapy: 1. It is performed within one week after the identification of ICC; 2. Day1 Oxaliplatin 85mg/m2 + gemcitabine 1g/m2, Day 8 gemcitabine 1g/m2; 3. Three weeks is a course of treatment; 4. A total of 3 courses. 2. Liver resection: It is performed 1 month after chemotherapy |
| Liver resection | No intervention | –Liver resection: It is performed within one week after the identification of ICC. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Sign written informed consent;
- Male or female patients aged 18-70;
- Eastern Cooperative Oncology Group (ECOG) score 0 points, Child-Pugh rating A;
- Clinically diagnosed as ICC as a potential entry, the neochemotherapy plus liver resection group must be histopathologically diagnosed as ICC before chemotherapy, and the liver resection alone group must be pathologically confirmed as intrahepatic cholangiocarcinoma after surgery;
- Resectable ICC patients with high risk of LN metastasis (Probability of LN metastasis ≥50% as evaluated by radiomics model);
Key exclusion criteria (16 listed)
- Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-biliary cell carcinoma malignant tumor components;
- Patients who have recurrent ICC after surgery, or have chemotherapy in the past;
- Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
- Active tuberculosis infection. Patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, no formal anti-tuberculosis treatment or tuberculosis is still active;
- Suffer from active, known or suspected autoimmune diseases. Subjects with hypothyroidism who only need hormone replacement therapy and skin diseases without systemic therapy can be selected;
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 |
|---|---|---|
| Neoadjuvant chemotherapyAlso: Preoperative chemotherapyNeoadjuvant chemotherapy with GEMOX regimen before liver resection | Drug | Neoadjuvant chemotherapy following liver section |
Primary outcome
Event-free survival
Time frame: 24 months
The time period from randomization to the occurrence of the following events: disease progression prevents liver resection; local or distant recurrence; second primary tumor; death due to various causes.
3 secondary outcomes
Overall survival
Time frame: 36 months
Objective response rate
Time frame: 4 months
Adverse events
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2020.
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neoadjuvant chemotherapy in people with Intrahepatic Cholangiocarcinoma Recurrent, run by Eastern Hepatobiliary Surgery Hospital.
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 9 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 21 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jun Li, M.D. (18930560396, lijundfgd1@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free survival (time frame: 24 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 21 Aug 2020.