Study of Immunotherapy Combined With Chemotherapy in Locally Advanced and Metastatic Pancreatic Cancer

Sponsor

Changhai Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04324307

Collaborator

(none)

Enrollment

Location

Arms

47.2

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the efficacy of PD-L1/CTLA4 BsAb for the second line treatment and the combination with chemotherapy for the first line treatment in pancreatic cancer

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced and Metastatic Pancreatic Cancer	Drug: PD-L1/CTLA4 BsAb Combination Product: GP Combination Product: FOLFIRINOX	Phase 1/Phase 2

Detailed Description

Subjects who signed the informed consent were assigned to three cohorts according to the actual treatment status. Cohort 1 enrolled subjects receiving PD-L1/CTLA4 BsAb 5mg/kg iv Q2W for 2nd treatment; cohort 2 enrolled subjects receiving PD-L1/CTLA4 BsAb in combination with gemcitabine/albumin- paclitaxel as 1st treatment for 4-6 cycles with PD-L1/CTLA4 BsAb monotherapy maintainence; cohort 3 enrolled subjects received systemic chemotherapy, receiving PD-L1/CTLA4 BsAb combined with oxaliplatin / irinotecan / leucovorin / fluorouracil (FOLFIRINOX) as 1st treatment for 4-6 cycles withPD-L1/CTLA4 BsAb monotherapy maintainence; until disease progression according to RECIST 1.1, intolerable toxicity, withdrawal, death, 2-yr treatment,who comes first.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter, Open-label Clinical Study of PD-L1/CTLA4 BsAb Combined With Chemotherapy in Locally Advanced and Metastatic Pancreatic Cancer

Actual Study Start Date :

Nov 26, 2019

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-L1/CTLA4 BsAb For 2nd line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W	Drug: PD-L1/CTLA4 BsAb PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W
Experimental: PD-L1/CTLA4 BsAb + GP For 1st line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W in combination with Gemcitabine 1000 mg/m2 and Nab-paclitaxel 125 mg/m2 , 28days/cycle	Drug: PD-L1/CTLA4 BsAb PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W Combination Product: GP Gemcitabine 1000mg/m2, iv, D1,8,15, 28days/cycle; nab-Paclitaxel 125mg/m2，iv，D1,8,15, 28days/cycle; Other Names: Gemcitabine nab-Paclitaxel
Experimental: PD-L1/CTLA4 BsAb + FOLFIRINOX For 1st line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W in combination with Oxaliplatin 68 or 85 mg/m2, Irinotecan 135 or 150 or 180 mg/m2, Calcium Folate 400 mg/m2, Fluorouracil 2400mg/m2, 14 days/cycle	Drug: PD-L1/CTLA4 BsAb PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W Combination Product: FOLFIRINOX Fluorouracil 2400mg/m2，iv，D1, 14days/cycle; Oxaliplatin 68-85mg/m2，iv, D1,14days/cycle;Irinotecan135-180mg/m2，iv, D1, 14days/cycle;Calcium Folate 400mg/m2，iv, D1, 14days/cycle; Other Names: Oxaliplatin Irinotecan Calcium Folate Fluorouracil

Arm

Intervention/Treatment

Experimental: PD-L1/CTLA4 BsAb

For 2nd line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W

Drug: PD-L1/CTLA4 BsAb

PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W

Experimental: PD-L1/CTLA4 BsAb + GP

For 1st line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W in combination with Gemcitabine 1000 mg/m2 and Nab-paclitaxel 125 mg/m2 , 28days/cycle

Drug: PD-L1/CTLA4 BsAb

PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W

Combination Product: GP

Gemcitabine 1000mg/m2, iv, D1,8,15, 28days/cycle; nab-Paclitaxel 125mg/m2，iv，D1,8,15, 28days/cycle;

Other Names:

Gemcitabine

nab-Paclitaxel

Experimental: PD-L1/CTLA4 BsAb + FOLFIRINOX

For 1st line treatment，PD-L1/CTLA4 BsAb 5mg/kg Q2W in combination with Oxaliplatin 68 or 85 mg/m2, Irinotecan 135 or 150 or 180 mg/m2, Calcium Folate 400 mg/m2, Fluorouracil 2400mg/m2, 14 days/cycle

Drug: PD-L1/CTLA4 BsAb

PD-L1/CTLA4 BsAb 5mg/kg, iv，Q2W

Combination Product: FOLFIRINOX

Fluorouracil 2400mg/m2，iv，D1, 14days/cycle; Oxaliplatin 68-85mg/m2，iv, D1,14days/cycle;Irinotecan135-180mg/m2，iv, D1, 14days/cycle;Calcium Folate 400mg/m2，iv, D1, 14days/cycle;

Other Names:

Oxaliplatin

Irinotecan

Calcium Folate

Fluorouracil

Outcome Measures

Primary Outcome Measures

ORR [2 years]
objective response rate

Secondary Outcome Measures

DCR [2 years]
Disease Control Rate
DOR [2 years]
Duration of Response
TTP [2 years]
Time to Response
PFS [2 years]
Progression Free Survival
OS [2 years]
Overall Survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histology or cytology confirmed as pancreatic ductal adenocarcinoma;
ECOG 0-1;
adequate organ function (absolute neutrophil count ≥1.5 x 109/L; platelet count ≥100 x 109/L; creatinine < 1.5 x ULN (upper normal) or calculated creatinine clearance ( CRCI) ≥ 60mL/min; albumin ≥ 30g/L; total bilirubin <1.5 x ULN; aspartate aminotransferase (AST) < 2.5 x ULN; alanine aminotransferase (ALT) < 2.5x ULN; INR or PT < 1.5x ULN, and aPTT <1.5x ULN);
no obvious symptoms of jaundice and ascites;
no other serious underlying diseases

Exclusion Criteria:

patients with active brain metastases;
history of autoimmune diseases, or need to be treated with corticosteroids and immunosuppressive agents;
past history of unstable angina, symptomatic congestive heart failure, severe arrhythmia, myocardial infarction within 6 months, QT interval prolongation (>450ms);
other malignant tumors within the last 5 years;
pregnant or lactating women;
NRS ≥ 4 points;
unintentional weight loss ≥ 5% within 1 month before the first dose even if peripheral or central vein nutrition support,