Trial Title:
Neoantigen Derived DCs as Cancer Treatment
NCT ID:
NCT05767684
Condition:
Refractory Tumor
Solid Tumor
Conditions: Official terms:
Neoplasms
Nivolumab
Lenvatinib
Conditions: Keywords:
immunotherapy
cancer vaccine
neoantigen
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
All patient will receive DCs monotherapy initially on day 1, 8, 15 and 29 as safety
run-in. Safety and efficacy (1st CT evaluation) will be conducted at day 43. On the 1st
CT evaluation, patient met randomization criteria and without progression disease/safety
concern will be randomized to either observation or booster of lenvatinib and nivolumab
during day 43 to 77.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Dendritic Cell Vaccine
Description:
Approximately 1.5 x 10^6±20% cells will be subcutaneously injected to the patient's
inguinal area (either left side or right side can be injected, only one area will be
injected each time) on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.
Arm group label:
Arm 1: DCs monotherapy
Arm group label:
Arm 2: DCs with booster of anti-VEGF/anti-PD-1.
Other name:
DCs
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
Lenvatinib 10mg/day on day 43-77
Arm group label:
Arm 2: DCs with booster of anti-VEGF/anti-PD-1.
Other name:
Lenvima
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Nivolumab 3mg/kg on day 43, 57 and 71.
Arm group label:
Arm 2: DCs with booster of anti-VEGF/anti-PD-1.
Other name:
OPDIVO
Summary:
Tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is safe and can
elicites remarkable T-cell responses but mostly did not really transfer into significant
clinical benefit. One possible reason is the lack of effective antigen and the
immunosuppressive microenvironment. Now we are exploring another new strategy, prediction
of neoantigen for priming DCs as cell-based therapy with or without booster of
anti-VEGF/anti-PD-1.
Detailed description:
The human immune system can recognize and destroy cancer cells but cancer cells are
capable of escaping from immune system by different ways, including the PD-1/PDL-1 axis
and the VEGF signaling pathway. The PD-1/PD-L1 axis represents an adaptive immune
resistance mechanism exerted by tumor cells. Previous study also revealed VEGF-A could
induce tumor-associated macrophages, Treg cells, and myeloid-derived suppressor cells,
creating an immunosuppressive microenvironment that prevent the maturation of dendritic
cells (DCs) and inhibit the activation of NK cells and T cells. Our research group
already completed some early phase clinical trials of DCs-based therapy, which
illustrated tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is
feasible and safe in patients with advanced colorectal cancer and lung cancer,
respectively. However, although DCs-based therapy elicited remarkable T-cell responses
but mostly did not really transfer into significant clinical benefit in previous study.
One possible reason is the lack of effective antigen and the immunosuppressive
microenvironment. Now we are exploring another new strategy, prediction of neoantigen for
priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- ≥20 years of age
- Provide written informed consent
- Histologically confirmed stage IV pancreatic cancer, liver cancer, biliary tract
cancer and colorectal cancer (excluding sarcoma and neuroendocrine tumor) that
refractory or intolerance to standard therapies for their condition (there is no
effective treatment by investigator judgement)
- Completed tumor and germline DNA and RNA sequencing and the neoantigen prediction
- Patients with chronic hepatitis B is eligible if receiving anti-hepatitis B agents
and the HBV DNA level < 2000 IU/ml prior to the preparation phase. Patients with
chronic hepatitis C are eligible if HCV RNA is undetectable (<15 IU/ml) prior to the
preparation phase
- Adequate organ function
- Absolute neutrophil count >1000/mcL
- Hemoglobin > 8.0 g/dl
- Platelet > 50000/mcL
- PT/aPTT < 1.5 x upper limit of normal (ULN)
- AST/ALT < 3 x ULN
- Bil(T) < 1.5 x ULN
- BUN/Cr < 1.5 x ULN
- Adequate immune system as defined by
- IgG > 614 mg/dl
- IgM > 53mg/dl
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Life expectancy at least>12weeks
- At least one measurable target lesion as defined by RECIST 1.1
Exclusion Criteria:
- Sarcoma、neuroendocrine tumor
- Last anticancer therapy administered within 2 weeks and any AEs should be ≤ grade 2
prior to leukapheresis
- Patients who cannot tolerate leukapheresis and follow-up blood sampling of 50ml at
day 43, day 85 and end-of- treatment.
- Any known active infection as judged by the investigator
- Any known chronic active infection of HIV, HTLV-1 or HTLV-2
- Requirement of systemic treatment with either corticosteroids (> 10 mg daily
prednisone equivalents) or other immunosuppressive medications within 14 days prior
to the screen phase. Inhaled or topical steroids and adrenal replacement doses > 10
mg daily prednisone equivalents are permitted in the absence of active autoimmune
disease.
- Other immunocompromising condition that in the opinion of the treating physician
renders the patient a poor candidate for this trial
- Pregnant women, nursing women, men or women of childbearing potential who are
unwilling to employ adequate contraception (condoms, diaphragm, birth control pills,
injections, intrauterine device (IUD), abstinence, etc.)
- Patients with history of penicillin allergy
- Other medical problems or conditions that, in the opinion of the investigator, would
make participation in the study hazardous for the patient
Gender:
All
Minimum age:
20 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Kaohsiung Medical University Hospital
Address:
City:
Kaohsiung
Country:
Taiwan
Status:
Not yet recruiting
Contact:
Last name:
Li-Tzong Chen, MD, PhD
Email:
leochen@nhri.edu.tw
Facility:
Name:
National Cheng-Kung University Hospital
Address:
City:
Tainan
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Yung-Yeh Su, MD
Phone:
+886-6-7000123
Phone ext:
65181
Email:
yysu@nhri.edu.tw
Facility:
Name:
National Institute of Cancer Research
Address:
City:
Tainan
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Yung-Yeh Su, MD
Phone:
+8867-7000123
Phone ext:
65181
Email:
yysu@nhri.edu.tw
Investigator:
Last name:
Li-Tzong Chen, MD, PhD
Email:
Principal Investigator
Start date:
June 1, 2023
Completion date:
March 30, 2026
Lead sponsor:
Agency:
National Health Research Institutes, Taiwan
Agency class:
Other
Collaborator:
Agency:
National Cheng-Kung University Hospital
Agency class:
Other
Source:
National Health Research Institutes, Taiwan
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05767684
