Clinical trial NCT06567600: Low-dose Gemcitabine and Cisplatin and PD-1/PD-L1 Antibody Therapy in Intrahepatic Cholangiocarcinoma
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Intrahepatic Cholangiocarcinoma
Chemotherapy Effect
Immunotherapy
Lead sponsor: Third Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital of Guangzhou Medical University
First posted: 2024-08-22
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: low-dose gemcitabine and cisplatin combined with PD-1/PD-L1 inhibitors
Primary purpose: TREATMENT

Brief 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.

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 \&quot;cold tumors\&quot;, and their unique immunosuppressive microenvironment is one of the reasons for the poor response rate to immunotherapy. Low-dose chemotherapy can transform \&quot;cold\&quot; tumors with low immunogenicity and poor immune cell infiltration into \&quot;hot\&quot; tumors with immune responsiveness and sufficient immune cell infiltration, enhance the effect of ICIs on tumor cells, and minimize systemic toxicity, thus preserving a \&quot;therapeutic window\&quot; 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years old, male or female;
2. Histopathologically confirmed intrahepatic cholangiocarcinoma;
3. TNM Staging≥Stage II (American Joint Committee on Cancer Prognostic Groups)
4. Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1);
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Child-Pugh score ≤ 7;
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;
8. The patient must be required to sign an informed consent form;

Exclusion Criteria:

1. 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;
2. 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;
3. 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;
4. Active infection requiring systemic therapy;
5. Human immunodeficiency virus (HIV) positive;
6. 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;
7. Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
8. 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;
9. Pregnant or lactating women;
10. Participated in other trials within the last 4 weeks;
11. Has a history of allergy to platinum;
12. 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 12 months
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: 12 months
measure: Deepness of response (DpR)
timeFrame: 12 months
measure: Disease control rate (DCR)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 36 months
measure: Progression-free Survival (PFS)
timeFrame: 36 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: The third affiliated hospital of SYSU
name: Ye Linsen, Professor
role: STUDY_CHAIR
References: