Pembrolizumab Plus Chemotherapy in 1st Line Treatment of Pancreatic Cancer

Sponsor

Seoul National University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04447092

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, phase 2 study of Pembrolizumab in combination with chemotherapy in chemotherapy-naïve advanced pancreatic cancer

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Cancer Chemotherapy Effect	Drug: Gemcitabine Drug: Nab-paclitaxel Drug: Pembrolizumab Drug: Oxaliplatin Drug: Leucovorin Drug: Irinotecan Drug: 5FU	Phase 2

Detailed Description

In unresectable advanced pancreatic cancer, palliative chemotherapy (mainly Gemcitabine/nab-Paclitaxel or FOLFIRINOX) is the mainstay of treatment. Regardless of the choice of first-line therapy, more than half of the patients with advanced/metastatic disease will progress within six months and will not survive more than one year.
Immune cells (IC) are a significant part of the pancreatic tumor-associated stroma and play a fundamental part in maintaining a non-immunogenic and immuno-suppressive environment.
IO (Immuno-Oncology drug) monotherapy is not effective in advanced pancreatic cancer; therefore, we need more active combination regimens including IO/IO or IO/chemotherapy, etc. Furthermore, we need biomarker study to uncover which population is an optimal target for this IO-based treatment strategy.
Based on these rationale, we plan to conduct an open-label, phase 2 study to explore biomarkers and evaluate the safety and efficacy of the pembrolizumab/chemotherapy combination in an advanced pancreatic cancer primary environment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

77 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Biomarker-oriented Study of Pembrolizumab in Combination With Chemotherapy in Chemotherapy -naïve Advanced Pancreatic Cancer

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Oct 1, 2021

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine/Nab-paclitaxel Gemcitabine/Nab-paclitaxel + pembrolizumab	Drug: Gemcitabine Gemcitabine 1000 mg/m2 iv D1, 8, 15 (every 4 weeks) Drug: Nab-paclitaxel Nab-paclitaxel 125 mg/m2 iv D1, 8, 15 (every 4 weeks) Drug: Pembrolizumab Pembrolizumab ( 200 ) mg iv D1 (every 3 weeks)
Experimental: FOLFIRINOX FOLFIRINOX + pembrolizumab	Drug: Pembrolizumab Pembrolizumab ( 200 ) mg iv D1 (every 3 weeks) Drug: Oxaliplatin Oxaliplatin 65 mg/m2 iv over 2 hours D1 (every 2 weeks) Drug: Leucovorin Leucovorin 400 mg/m2 iv D1 (every 2 weeks) Drug: Irinotecan Irinotecan 140 mg/m2 iv over 1.5 hours D1 (every 2 weeks) Drug: 5FU 5-FU 2400 mg/m2 iv over 46 hours D1 (every 2 weeks)

Arm

Intervention/Treatment

Experimental: Gemcitabine/Nab-paclitaxel

Gemcitabine/Nab-paclitaxel + pembrolizumab

Drug: Gemcitabine

Gemcitabine 1000 mg/m2 iv D1, 8, 15 (every 4 weeks)

Drug: Nab-paclitaxel

Nab-paclitaxel 125 mg/m2 iv D1, 8, 15 (every 4 weeks)

Drug: Pembrolizumab

Pembrolizumab ( 200 ) mg iv D1 (every 3 weeks)

Experimental: FOLFIRINOX

FOLFIRINOX + pembrolizumab

Drug: Pembrolizumab

Pembrolizumab ( 200 ) mg iv D1 (every 3 weeks)

Drug: Oxaliplatin

Oxaliplatin 65 mg/m2 iv over 2 hours D1 (every 2 weeks)

Drug: Leucovorin

Leucovorin 400 mg/m2 iv D1 (every 2 weeks)

Drug: Irinotecan

Irinotecan 140 mg/m2 iv over 1.5 hours D1 (every 2 weeks)

Drug: 5FU

5-FU 2400 mg/m2 iv over 46 hours D1 (every 2 weeks)

Outcome Measures

Primary Outcome Measures

Objective Response Rate [8 weeks]
The percentage of patients whose optimal response achieves CR or PR between the initial response assessment and the time between treatment termination or intermediate dropout due to any cause

Secondary Outcome Measures

Progression-free survival [8 weeks]
Time from enroll until disease progression or death
Duration of response [8 weeks]
Time from enroll untill disease progression or death in patients whose optimal response achieves CR or PR
Disease control rate [8 weeks]
The percentage of patients who have achieved complete response, partial response and stable disease
Overall survival [8 weeks]
Time from enroll until death from any cause
Immune-related response [8 weeks]
RECIST 1.1, ir response

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male/female participants who are at least 18 years of age on the day of signing informed consent
Histologically confirmed diagnosis of unresectable, recurrent, or metastatic pancreatic cancer
Not pregnant, not breasfeeding, and agree to use proper contraception,
Chemotherapy-naïve for advanced pancreatic cancer (previous adjuvant chemotherapy is allowed)
Have measurable disease based on RECIST 1.1.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Have adequate organ function

Haemoglobin ≥ 9.0 g/dL
Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)
Platelet count ≥ 100 x 109/L (>75,000 per mm3)
Serum creatinine CL>30 mL/min by the Cockcroft-Gault formula or serum creatinine ≤1.5 × ULN
Serum bilirubin ≤ 1.5 x ULN
AST (SGOT)/ALT (SGPT) ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤ 5x ULN
International normalized ratio (INR) or Prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy

Exclusion Criteria:

A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks
Has received prior radiotherapy within 2 weeks of start of study treatment.
Has received a live vaccine within 30 days prior to the first dose of study drug.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Has known active CNS metastases and/or carcinomatous meningitis.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has an active infection requiring systemic therapy.
Has a known history of Human Immunodeficiency Virus (HIV).
Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
Has a known history of active TB (Bacillus Tuberculosis).
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.