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

Phase 2

• Conditions: Metastatic Pancreatic Cancer
• Interventions: Drug: Donafenib; Drug: S1

• Registration Number: NCT05138159
• Lead Sponsor: Fudan University

Brief 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.

Detailed 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.

Study Timeline

• Status Verified: 2021-10
• Study First Submitted: 2021-11-17
• Study First Submitted QC: 2021-11-17
• Last Update Submitted: 2021-11-17
• Study First Posted: 2021-11-30
• Last Update Posted: 2021-11-30
• Study Start: 2021-12-01
• Primary Completion: 2023-05-30
• Study Completion: 2023-07-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: Donafenib + S-1	S1	Donafenib: 200mg po bid； 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.
Experimental: Donafenib + S-1	Donafenib	Donafenib: 200mg po bid； 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.

Primary Outcome Measures

Name	Time	Method
Overall Survival	through study completion, an average of 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	through study completion, an average of 1 year	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.
Overall Response Rate	through study completion, an average of 1 year	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.
Incidence of Adverse Events	through study completion, an average of 1 year	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.

Trial Locations

Locations (1)

Fudan University; 🇨🇳 Shanghai, China