Refractory TumorPhase 1NCT05767684
Neoantigen Derived DCs as Cancer Treatment
A Phase 1 study testing Dendritic Cell Vaccine, Lenvatinib and Nivolumab in people with Refractory Tumor and Solid Tumor, run by National Health Research Institutes, Taiwan at 3 sites in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Refractory Tumor, Solid Tumor
- What is being tested?
- Dendritic Cell Vaccine, Lenvatinib and Nivolumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesTaiwan
- Study dates
- 1 Jun 2023to 30 Mar 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 1 country.
Taiwan3 sites, 3 recruiting
- Not yet recruiting
Kaohsiung Medical University Hospital
Kaohsiung City
Li-Tzong Chen, MD, PhD, leochen@nhri.edu.tw
- Recruiting
National Cheng-Kung University Hospital
Tainan
Yung-Yeh Su, MD, +886-6-7000123 ext. 65181, yysu@nhri.edu.tw
- Recruiting
National Institute of Cancer Research
Tainan
Yung-Yeh Su, MD, +8867-7000123 ext. 65181, yysu@nhri.edu.tw
Li-Tzong Chen, MD, PhD
About this study
Official title: Personalized Neoantigen Derived Dendritic Cell-Based Immunotherapy as Cancer Treatment
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.
Read the 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.
- Conditions
- Refractory Tumor, Solid Tumor
- Being tested
- Dendritic Cell Vaccine, Lenvatinib, Nivolumab
- Keywords
- immunotherapy, cancer vaccine, neoantigen
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic Cell VaccineBiological
Also called DCs
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.
LenvatinibDrug
Also called Lenvima
Lenvatinib 10mg/day on day 43-77
NivolumabDrug
Also called OPDIVO
Nivolumab 3mg/kg on day 43, 57 and 71.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: DCs monotherapy | Experimental | DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309. Receives: Biological: Dendritic Cell Vaccine |
| Arm 2: DCs with booster of anti-VEGF/anti-PD-1. | Experimental | DCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309 plus lenvatinib 10mg QD on day 43-77 and nivolumab 3mg/kg on day 43, 57 and 71. Receives: Biological: Dendritic Cell Vaccine; Drug: Lenvatinib; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects experienced limiting toxicities in the first 6 weeks.
The following toxicities that happened during first 6 weeks are considered LTs. Toxicities are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0:
- >=Grade 3 non-hematological toxicity
- >=Grade 4 hematological toxicity
- Any death not clearly due to the underlying disease or extraneous causes.
- Any case meeting Hy's law
- Recurrent grade 2 pneumonitis
Measured: 6 weeks
Secondary outcomes (3)
Percentage of patients who had a clinical response
Response was assessed by the iRECIST.
Measured: 1 year
Number of participants who did not progressed or survived at 1 year
1 year progression-free survival and overall survival rate
Measured: 1 year
Number of subjects experienced any ≥ grade 3 toxicities.
any ≥ grade 3 toxicities rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2023
- Study start1 Jun 2023
- Primary completion30 Mar 2025 (estimated)
- Study completion30 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- National Cheng-Kung University Hospital
- Responsible party
- Sponsor
- Investigators
- Li-Tzong Chen, MD, PhD, Principal investigator, Kaohsiung Medical University Hospital, and Center for Cancer Research, Kaohsiung Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05767684
- Sponsor's protocol ID
- A-BR-108-087
- Status last verified
- Feb 2023
- First submitted
- 2 Mar 2023
- Last updated
- 25 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Personalized Neoantigen Derived Dendritic Cell-Based Immunotherapy as Cancer Treatment
- ClinicalTrials.gov ID
- NCT05767684
- Acronym / sponsor ID
- A-BR-108-087
- Conditions
- Refractory Tumor, Solid Tumor
- Keywords
- immunotherapy, cancer vaccine, neoantigen
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Cheng-Kung University Hospital
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 30 Mar 2025 (estimated)
- Study completion
- 30 Mar 2026 (estimated)
- First posted
- 14 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Arm 1: DCs monotherapy | Experimental | Biological: Dendritic Cell VaccineDCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309. |
| Arm 2: DCs with booster of anti-VEGF/anti-PD-1. | Experimental | Biological: Dendritic Cell Vaccine, Drug: Lenvatinib, Drug: NivolumabDCs injection on day 1, 8, 15, 29, 85, 141, 197, 253 and 309 plus lenvatinib 10mg QD on day 43-77 and nivolumab 3mg/kg on day 43, 57 and 71. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- ≥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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dendritic Cell VaccineAlso: DCsApproximately 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. | Biological | Arm 1: DCs monotherapy, Arm 2: DCs with booster of anti-VEGF/anti-PD-1. |
| LenvatinibAlso: LenvimaLenvatinib 10mg/day on day 43-77 | Drug | Arm 2: DCs with booster of anti-VEGF/anti-PD-1. |
| NivolumabAlso: OPDIVONivolumab 3mg/kg on day 43, 57 and 71. | Drug | Arm 2: DCs with booster of anti-VEGF/anti-PD-1. |
Primary outcome
Number of subjects experienced limiting toxicities in the first 6 weeks.
Time frame: 6 weeks
The following toxicities that happened during first 6 weeks are considered LTs. Toxicities are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: * >=Grade 3 non-hematological toxicity * >=Grade 4 hematological toxicity * Any death not clearly due to the underlying disease or extraneous causes. * Any case meeting Hy's law * Recurrent grade 2 pneumonitis
3 secondary outcomes
Percentage of patients who had a clinical response
Time frame: 1 year
Number of participants who did not progressed or survived at 1 year
Time frame: 1 year
Number of subjects experienced any ≥ grade 3 toxicities.
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li-Tzong Chen, MD, PhD principal investigator
Kaohsiung Medical University Hospital, and Center for Cancer Research, Kaohsiung Medical University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dendritic Cell Vaccine, Lenvatinib and Nivolumab in people with Refractory Tumor and Solid Tumor, run by National Health Research Institutes, Taiwan at 3 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yung-Yeh Su, MD (+886-6-7000123 ext. 65181, yysu@nhri.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects experienced limiting toxicities in the first 6 weeks. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2023.