Locally Advanced Pancreatic Cancer, Metastatic Pancreatic Cancer
Conditions
Keywords
Locally advanced pancreatic cancer, Metastatic pancreatic cancer, SHR-1701, Apatinib, GnP
Brief summary
The goal of this clinical trial is to evaluate the safety and efficacy of GnP combined with SHR-1701 and Apatinib as first-line treatment in patients with locally advanced or metastatic pancreatic ductal adenocarcinoma.
Detailed description
This study is a prospective, single-arm, single-center, phase Ib/II clinical trial evaluating the safety and efficacy of GnP combined with SHR-1701 and Apatinib as first-line treatment in patients with locally advanced or metastatic pancreatic cancer.
Interventions
DRUGSHR-1701
SHR-1701 is administered by intravenous infusion at a dose of 30 mg/kg once every 3 weeks (Q3W). The dose may be adjusted to the recommended phase II dose (RP2D) determined during the phase Ib safety run-in phase.
DRUGApatinib
Apatinib is administered orally at a dose of 250 mg once daily (QD). The dose may be adjusted to the recommended phase II dose (RP2D) determined during the phase Ib safety run-in phase.
DRUGgemcitabine
Gemcitabine is administered by intravenous infusion at a dose of 1000 mg/m² on days 1 and 8 of each 3-week cycle.
DRUGNab-paclitaxel
Nab-paclitaxel is administered by intravenous infusion at a dose of 125 mg/m² on days 1 and 8 of each 3-week cycle.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1\) Age 18-75 years, regardless of sex; 2) patients with histologically confirmed pancreatic ductal adenocarcinoma (PDAC); 3) previously untreated patients with unresectable locally advanced or metastatic PDAC, with at least one measurable lesion according to RECIST v1.1, and target lesions must not have received prior radiotherapy or local treatment; 4) ECOG performance status of 0-1; 5) life expectancy ≥3 months; 6) willingness to comply with study procedures and able to receive treatment and undergo follow-up; 7) adequate major organ function, with laboratory test results meeting the following criteria within 7 days before enrollment: white blood cell (WBC) count ≥2.5×10⁹/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet (PLT) count ≥75×10⁹/L, hemoglobin (HGB) ≥90 g/L (without blood transfusion or erythropoietin \[EPO\] dependence within 7 days), total bilirubin (TBIL) ≤1.5× the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5×ULN, albumin ≥30 g/L, international normalized ratio (INR) ≤1.5×ULN, serum creatinine (Cr) ≤1.5×ULN, and urinary protein ≤1+; 8) patients who are hepatitis B surface antigen (HBsAg)-positive with a peripheral blood hepatitis B virus DNA (HBV-DNA) level ≤1×10³/L; patients who are HBsAg-positive with a peripheral blood HBV-DNA level ≥1×10³/L may also be eligible if, in the investigator's judgment, chronic hepatitis B is clinically stable and does not increase the patient's risk; 9) voluntary participation in the study and provision of written informed consent.
Exclusion criteria
1\) Known hypersensitivity to any study drug; 2) known or suspected central nervous system metastases, defined as signs or symptoms suggestive of CNS metastasis, unless CNS metastasis has been excluded by CT or MRI; 3) history of other malignancies within 5 years, except adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix; 4) requiring any concomitant anticancer treatment other than the study treatment during the study, including chemotherapy, targeted therapy, hormonal therapy, immunotherapy, radiotherapy, or traditional Chinese medicine with antitumor activity; 5) prior or current treatment with chemotherapy, FAK inhibitors, or antibodies targeting PD-1, PD-L1, PD-L2, CD137, or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), including ipilimumab or any other antibody or drug targeting T-cell costimulatory or checkpoint pathways; 6) diagnosis of immunodeficiency or chronic systemic corticosteroid therapy (prednisone \>10 mg/day or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment; 7) receipt of a live vaccine within 30 days before the first dose of study treatment, including but not limited to measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccines; inactivated seasonal influenza vaccines are permitted, whereas live attenuated vaccines such as intranasal influenza vaccines (e.g., FluMist) are not permitted; 8) uncontrolled hypertension, defined as systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg despite treatment; 9) significant cardiac disease, including congestive heart failure (NYHA class III-IV), previous myocardial infarction, or uncontrolled angina within 6 months; 10) clinically significant arrhythmias requiring treatment, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation, or ECG abnormalities confirmed on repeat examination that, in the investigator's judgment, require clinical intervention or treatment; 11) history of hemorrhagic or thromboembolic events within the past 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or spontaneous major tumor-related bleeding; 12) surgery required within 28 days before or anticipated within 28 days after the last dose of study treatment; 13) uncontrolled third-space fluid accumulation, such as large pleural effusion or ascites; 14) definite gastrointestinal bleeding tendency within 4 weeks before the first dose, including: ① active localized ulcerative lesions with positive fecal occult blood; ② melena or hematemesis within 28 days; or ③ positive fecal occult blood in patients with unresected tumor invasion of the gastrointestinal tract who, in the opinion of the principal investigator at the study center, may be at risk of major gastrointestinal bleeding; 15) previous gastrointestinal perforation or suspected risk of gastrointestinal perforation, or intestinal obstruction; 16) concomitant medications that, in the investigator's judgment, are required during the trial and may affect the metabolism of the investigational drug, such as strong CYP3A4 inhibitors or inducers, or drugs with a narrow therapeutic index that are primarily metabolized by CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2D6; 17) severe psychiatric disorders; 18) women who are pregnant, breastfeeding, or potentially pregnant; 19) women or men of childbearing potential unwilling to use effective contraception during the study and for 3 months after the last dose of study treatment; 20) participation in another clinical trial of a drug or medical device within 4 weeks before enrollment; 21) any other condition that, in the investigator's judgment, makes the patient unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase II Dose (RP2D) | through phase I study completion, an average of 5 months | RP2D will be determined on the basis of evaluation on safety and efficacy data in Phase Ib. |
| Objective Response Rate (ORR) | through study completion, an average of 2 years | Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | through study completion, an average of 2 years | Time from the first administration of study treatment to death from any cause. Participants who are alive or lost to follow-up at the time of analysis will be censored at the date of their last known survival assessment. |
| Progression-Free Survival (PFS) | through study completion, an average of 2 years | Time from the first administration of study treatment to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first. Participants who are alive and have not experienced disease progression will be censored at the date of the last tumor assessment. |
| Disease Control Rate (DCR) | through study completion, an average of 2 years | Proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) as the best overall response according to RECIST v1.1 criteria. |
| Duration of Response (DOR) | through study completion, an average of 2 years | Time from the first documented complete response (CR) or partial response (PR) to the first documented disease progression according to RECIST v1.1 or death from any cause, whichever occurs first. |
| Time to Progression (TTP) | through study completion, an average of 2 years | Time from the first administration of study treatment to the first documented disease progression according to RECIST v1.1 in the ITT population. Participants who have not experienced disease progression at the time of analysis will be censored at the date of the last tumor assessment. |
| R0 Resection Rate | through study completion, an average of 2 years | Proportion of participants in the ITT population who undergo surgical resection and achieve R0 resection, defined as complete macroscopic tumor removal with no microscopic residual tumor at the resection margin. |
| Incidence of Treatment-Related Adverse Events (TRAEs) | through study completion, an average of 2 years | Incidence and severity of adverse events considered by the investigator to be related to study treatment, graded according to NCI-CTCAE version 5.0. |
| Incidence of Serious Adverse Events (SAEs) | through study completion, an average of 2 years | Incidence of serious adverse events, including events resulting in death, life-threatening events, hospitalization or prolongation of hospitalization, persistent or significant disability, congenital anomaly, or other medically important events. |
Countries
China
Contacts
CONTACTDan Cao
CONTACTMin Ren
PRINCIPAL_INVESTIGATORDan Cao
Division of Abdominal Tumor, Department of Medical Oncology, Cancer Center and State Key Laboratory of Biological Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan
Outcome results
None listed