Intrahepatic CholangiocarcinomaPhase 2NCT06567600
Low-dose Gemcitabine and Cisplatin and PD-1/PD-L1 Antibody Therapy in Intrahepatic Cholangiocarcinoma
A Phase 2 study testing Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody in people with Intrahepatic Cholangiocarcinoma and Chemotherapy Effect, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
Trial summary
In this phase 2 study, researchers aimed to evaluate the efficacy and safety of low-dose gemcitabine and cisplatin chemotherapy and the immune checkpoint inhibitor PD-1/PD-L1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intrahepatic Cholangiocarcinoma, Chemotherapy Effect, Immunotherapy
- What is being tested?
- Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2024to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Age ≥ 18 years old, male or female;
- Histopathologically confirmed intrahepatic cholangiocarcinoma;
- TNM Staging≥Stage II (American Joint Committee on Cancer Prognostic Groups)
- Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1);
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Child-Pugh score ≤ 7;
- Adequate organ function (neutrophil count of ≥1.5×10^9 cells/L, hemoglobin concentrations of ≥90 g/L, platelet cell count of ≥100×10^9 cells/L, bilirubin ≤1.5×ULN, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 5×ULN, serum creatinine ≤ 1.5 x ULN, Thyroid stimulating hormone (TSH) ≤ 1 x ULN;
- The patient must be required to sign an informed consent form;
Who cannot join
- Patients who have received previous treatment with interventional therapy, radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy (PD-1, PD-L1, CLTA-4 antibody, etc), or surgery within the last 2 months;
- Patients with other malignant tumors within the last 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
- Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active;
- Active infection requiring systemic therapy;
- Human immunodeficiency virus (HIV) positive;
- Have an active, known, or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled;
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- Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
- Abnormal blood coagulation (INR >1.5, or PT>ULN+4s, or APTT >1.5 x ULN), with a bleeding tendency or receiving thrombolytic or anticoagulant therapy;
- Pregnant or lactating women;
- Participated in other trials within the last 4 weeks;
- Has a history of allergy to platinum;
- Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined treatment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The Third Affiliated Hospital of Sun Yat-Sen University
Guangzhou, Guangdong
About this study
Official title: Combined Therapy Using Low-dose Gemcitabine and Cisplatin Chemotherapy and PD-1/PD-L1Antibody for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: an Open-label, Multicenter, Single-arm Clinical Trial
In this phase 2 study, researchers aimed to evaluate the efficacy and safety of low-dose gemcitabine and cisplatin chemotherapy and the immune checkpoint inhibitor PD-1/PD-L1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma.
Read the detailed description
More and more studies suggest that low-dose chemotherapy has the ability to reshape the tumor microenvironment and promote tumor immunotherapy in a variety of tumors, supporting the rationality of combining low-dose chemotherapy with immunotherapy to effectively treat tumors with low T cell infiltration. More than half of intrahepatic cholangiocarcinomas are non-inflammatory \"cold tumors\", and their unique immunosuppressive microenvironment is one of the reasons for the poor response rate to immunotherapy. Low-dose chemotherapy can transform \"cold\" tumors with low immunogenicity and poor immune cell infiltration into \"hot\" tumors with immune responsiveness and sufficient immune cell infiltration, enhance the effect of ICIs on tumor cells, and minimize systemic toxicity, thus preserving a \"therapeutic window\" for combined immunotherapy/targeted therapy. Preclinical and clinical studies have shown that it is necessary to study the optimal dose of chemotherapeutic drugs in combination therapy. In combination therapy, long-term, adequate doses of chemotherapeutic drugs may be unnecessary because this will not only lead to more severe toxicity, but also damage rather than enhance anti-tumor immunity.
To determine the efficacy and safety of low-dose chemotherapy combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma, we designed an open-label, prospective, multicenter, single-arm clinical study of low-dose gemcitabine + cisplatin combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma.
- Being tested
- Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1AntibodyDrug
Also called LDGC-PB
Low-dose Gemcitabine and Cisplatin Chemotherapy:
Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles
PD-1/PD-L1Antibody:
Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met.
| Study group | Role | What they receive |
|---|---|---|
| Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody | Experimental | Low-dose Gemcitabine and Cisplatin Chemotherapy:
Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles
PD-1/PD-L1Antibody:
Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met. Receives: Drug: Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR according to RECIST 1.1 using investigator assessment
Measured: 12 months
Secondary outcomes (5)
Incidence of adverse events
Rate of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 12 months
Deepness of response (DpR)
DpR according to RECIST 1.1 using investigator assessment
Measured: 12 months
Disease control rate (DCR)
DCR according to RECIST 1.1 using investigator assessment
Measured: 12 months
Overall Survival (OS)
OS is defined as the time from date of combined theray start to the date of death from any cause or to the date of last follow-up if patients are alive
Measured: 36 months
Progression-free Survival (PFS)
From the beginning date of combined therapy to the date of disease progression. PFS according to RECIST 1.1 using investigator assessment
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2024
- Study start1 Sep 2024 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intrahepatic CholangiocarcinomaStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- low-dose gemcitabine and cisplatin combined with PD-1/PD-L1 inhibitors
- Masking
- None (open label)
- Enrolment
- 43 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Linsen Ye, Third Affiliated Hospital, Sun Yat-Sen University
- Investigators
- Ye Linsen, Professor, Study chair, The third affiliated hospital of SYSU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06567600
- Sponsor's protocol ID
- ZSSY-2407
- Status last verified
- Aug 2024
- First submitted
- 20 Aug 2024
- Last updated
- 22 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Therapy Using Low-dose Gemcitabine and Cisplatin Chemotherapy and PD-1/PD-L1Antibody for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: an Open-label, Multicenter, Single-arm Clinical Trial
- ClinicalTrials.gov ID
- NCT06567600
- Acronym / sponsor ID
- ZSSY-2407
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 43 participants (estimated)
- Lead sponsor
- Third Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Collaborators
- Second Affiliated Hospital of Guangzhou Medical University
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 22 Aug 2024 (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.
In this phase 2 study, researchers aimed to evaluate the efficacy and safety of low-dose gemcitabine and cisplatin chemotherapy and the immune checkpoint inhibitor PD-1/PD-L1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma.
Detailed description
More and more studies suggest that low-dose chemotherapy has the ability to reshape the tumor microenvironment and promote tumor immunotherapy in a variety of tumors, supporting the rationality of combining low-dose chemotherapy with immunotherapy to effectively treat tumors with low T cell infiltration. More than half of intrahepatic cholangiocarcinomas are non-inflammatory \"cold tumors\", and their unique immunosuppressive microenvironment is one of the reasons for the poor response rate to immunotherapy. Low-dose chemotherapy can transform \"cold\" tumors with low immunogenicity and poor immune cell infiltration into \"hot\" tumors with immune responsiveness and sufficient immune cell infiltration, enhance the effect of ICIs on tumor cells, and minimize systemic toxicity, thus preserving a \"therapeutic window\" for combined immunotherapy/targeted therapy. Preclinical and clinical studies have shown that it is necessary to study the optimal dose of chemotherapeutic drugs in combination therapy. In combination therapy, long-term, adequate doses of chemotherapeutic drugs may be unnecessary because this will not only lead to more severe toxicity, but also damage rather than enhance anti-tumor immunity.
To determine the efficacy and safety of low-dose chemotherapy combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma, we designed an open-label, prospective, multicenter, single-arm clinical study of low-dose gemcitabine + cisplatin combined with PD-1/PD-L1 inhibitors in the treatment of patients with advanced intrahepatic cholangiocarcinoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- low-dose gemcitabine and cisplatin combined with PD-1/PD-L1 inhibitors
| Arm | Type | Receives |
|---|---|---|
| Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody | Experimental | Drug: Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1AntibodyLow-dose Gemcitabine and Cisplatin Chemotherapy: Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles PD-1/PD-L1Antibody: Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years old, male or female;
- Histopathologically confirmed intrahepatic cholangiocarcinoma;
- TNM Staging≥Stage II (American Joint Committee on Cancer Prognostic Groups)
- Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1);
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (12 listed)
- Patients who have received previous treatment with interventional therapy, radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy (PD-1, PD-L1, CLTA-4 antibody, etc), or surgery within the last 2 months;
- Patients with other malignant tumors within the last 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
- Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active;
- Active infection requiring systemic therapy;
- Human immunodeficiency virus (HIV) positive;
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 |
|---|---|---|
| Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1AntibodyAlso: LDGC-PBLow-dose Gemcitabine and Cisplatin Chemotherapy: Gemcitabine 500 mg/m2 Cisplatin 12.5 mg/m2 on day 1 and day 8 of each 21-day cycle for up to eight cycles PD-1/PD-L1Antibody: Pembrolizumab 200mg on day 1 of each 21-day cycle Durvalumab 1500 mg on day 1 of each 21-day cycle After completion of gemcitabine and cisplatin, 200mg of Pembrolizumab or 1500 mg of Durvalumab may administer once every 3 or 4 weeks until clinical or imaging (per RECIST v1.1) disease progression or until unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria were met. | Drug | Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody |
Primary outcome
Objective Response Rate (ORR)
Time frame: 12 months
ORR according to RECIST 1.1 using investigator assessment
5 secondary outcomes
Incidence of adverse events
Time frame: 12 months
Deepness of response (DpR)
Time frame: 12 months
Disease control rate (DCR)
Time frame: 12 months
Overall Survival (OS)
Time frame: 36 months
Progression-free Survival (PFS)
Time frame: 36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
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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.
Ye Linsen, Professor study chair
The third affiliated hospital of SYSU
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 Low-dose Gemcitabine and Cisplatin Chemotherapy plus PD-1/PD-L1Antibody in people with Intrahepatic Cholangiocarcinoma and Chemotherapy Effect, run by Third Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
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 8 inclusion and 12 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: opening soon, as of the sponsor's last update on 22 Aug 2024. 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 China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ye Linsen (+86 17502060927, ye_linsen@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (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 22 Aug 2024.