A Study of Donafenib Plus S-1 in Treating Patients With Metastatic Pancreatic Cancer After Chemotherapy With Nab-paclitaxel Plus Gemcitabine Regimen

Metastatic Pancreatic Cancer Clinical Trial

Official title:

A Prospective, Phase II, Single-arm Study to Evaluate The Safety and Efficacy of Donafenib Plus S-1 in Treating Patients With Metastatic Pancreatic Cancer After Chemotherapy With Nab-paclitaxel Plus Gemcitabine Regimen

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05138159
• Other study ID #: PDAC-ZPS-S
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 1, 2021
• Est. completion date: July 30, 2023

Study information

• Verified date: October 2021
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single arm, open label Phase II clinical trial to evaluate the efficacy and safety of donafenib combined with S-1 in treating Patients with metastatic pancreatic cancer after chemotherapy with Nab-paclitaxel plus gemcitabine regimen.

Description:

While NG ( Nab-paclitaxel + gemcitabine) is one of the preferred first-line chemotherapy for metastatic pancreatic cancer, we have to investigate possible therapeutic options after NG regimen. In this single arm, open-label clinical trial, metastatic pancreatic cancer patients will be received donafenib and S-1. Treatment repeats every 3 weeks until the disease recurrence or unacceptable toxicity, death or begin a novel therapeutic. The efficacy and safety data will be assessed through OS, ORR, DCR, PFS,TTP and adverse effects as graded by NCI CTC-AE 5.0.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: July 30, 2023
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Informed consent and willing to complete the study according to the protocol.
• Age = 18 years and = 75 years, and there is no limit on the gender
• ECOG performance scale 0-1;
• Diagnosed as pancreatic adenocarcinoma by histology and cytology;
• Treatment of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen(The disease progresses during the course of treatment or within 6 months after the end of treatment, with clear imaging evidence; this does not include patients with intolerable toxicity);
• Baseline blood routine and biochemical indexes meet the following criteria:

1. Blood routine examination criteria must be met: (no blood transfusion within 14 days)

1. HB=90g/L;

2. ANC=1.5×109/L;

3. PLT=100×109/L.

2. Biochemical tests are subject to the following criteria:

1. BIL <1.25xULN ;

2. ALT and AST<2.5ULN;

3. Serum creatinine. Less than 1.5 times the upper limit of normal value, Endogenous creatinine clearance>60ml/min ( Cockcroft-Gault formula).

4. Albumin=28g/L.

3. Blood coagulation indexes are subject to the following criteria:

1. Prothrombin time (PT) and international normalized ratio (INR) =1.5 × ULN;

2. Activated partial thromboplastin time(APTT)=1.5 × ULN.

• According to the standard of RECIST 1.1, there is at least one imaging measurable lesion;
• Life expectancy = 3 months;
• Patients and their families were willing to cooperate with follow-up.

Exclusion Criteria:

• Diagnosis of malignant diseases other than pancreatic cancer within 5 years prior to first administration (excluding cured skin basal cell carcinoma, squamous carcinoma of the skin, and/or resected carcinoma in situ);
• Medical conditions that affect absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.);
• Patients with brain metastases or pial metastases;
• Patients with a clear past history of neurological or psychiatric disorders, including epilepsy or dementia;
• Comorbidities (e.g., severe or uncontrolled hypertension, severe diabetes, and/or thyroid disease) that, in the investigator's judgment, seriously endanger patients' safety or prevent them from completing the study;
• The patient was currently participating in an interventional clinical study or had been treated with another study drug or study device in the 4 weeks prior to initial dosing;
• The patient had a history of organ transplantation;
• Concurrent administration of drugs that may prolong QTc and/or induce Tdp;
• Patients also take drugs that affect drug metabolism;
• HIV infection or acute or chronic viral hepatitis (hbSAG positive, HBV-DNA load =500IU/ml and/or HCV antibody positive);
• Excluded patients with serious cardiovascular disease, including grade =II cardiac dysfunction (NYHA criteria);
• Patients with severe gastrointestinal dysfunction (bleeding, infection, obstruction, or diarrhea greater than grade 1) were excluded;
• Patients with abnormal coagulation function, bleeding tendency, or receiving thrombolytic or anticoagulant therapy were excluded;
• Patients with a severe arterial thromboembolism event within 6 months were excluded;
• Excluding women who are pregnant or breast-feeding.

Related Conditions & MeSH terms

• Metastatic Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Donafenib
Donafenib: 200mg po bid.
• S1
S-1 capsule: According to the body surface area <1.25m2 40mg/d, 1.25 ~ 1.5 m2 50 mg/d, > 1.5m2 60mg/d po bid, taking 14 days, stopping for 7 days, 21 days for 1 cycle.

Locations

Country	Name	City	State
China	Fudan University	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	To evaluate the overall survival of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib combined with S-1.	through study completion, an average of 1 year
Secondary	Progression Free Survival	To investigate the progression-free survival (PFS) of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib combined with S-1.	through study completion, an average of 1 year
Secondary	Overall Response Rate	To evaluate the overall response rate of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib combined with S-1.	through study completion, an average of 1 year
Secondary	Incidence of Adverse Events	Adverse events of patients with advanced metastatic pancreatic cancer who have failed with NG (Nab-paclitaxel + gemcitabine) regimen after treatment with Donafenib plus S-1.	through study completion, an average of 1 year