TSA-DC Vaccine in Treating Patients With Gastrointestinal Solid Tumor
Primary Purpose
Tumor Gastric, Tumor, Colorectal
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Tumor Specific Antigen-loaded Dendritic Cells
Cyclophosphamide
Sponsored by
About this trial
This is an interventional treatment trial for Tumor Gastric
Eligibility Criteria
Inclusion Criteria:
- Be ≥18 and ≤75,no gender based;
- Expression of HLA-A0201/1101/2402;
- Histopathologic documentation of gastrointestinal solid tumors(stomach cancer or colorectal cancer ) concurrent with the diagnosis of metastatic disease, and the tumor is Measurable;
- Patients must have adequate tissue (fresh or paraffin block) for DNA extraction, which is used for gene sequencing, and prognoses the tumor specific antigen in turn,can predict to have new tumor antigens with high affinity for MHC molecules;
- Failure in conventional treatment, or though benefit from chemotherapy the patient can't tolerant subjectively;
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 and an anticipate life expectancy of at least three months,be cooperate to adverse reactions monitoring and therapeutic evaluation of the treatment;
- Participants of child-bearing potential must agree to use adequate contraceptive methods up to 12 months after the pretreatment;
- Serology:Seronegative for HIV antibody,seronegative for hepatitis C antibody. Hematology:Absolute neutrophil count ≥ 1000/mm(3) without the support of filgrastim ,WBC ≥ 3000/mm(3),lymphocyte count ≥ 800/mm(3),Platelet count ≥ 100,000/mm(3),Hemoglobin ≥ 9.0 g/dl Chemistry:Serum ALT/AST ≤ 2.5 times the upper limit of normal,Serum Creatinine ≤1.6 mg/dl,Total bilirubin < 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dl;
- Patients or their legal representatives are willing and able to understand and written informed consent form for the trial;
Exclusion Criteria:
- Is pregnant or breastfeeding,or expecting to conceive;
- Have a history of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Suffered grade 3-4 major organ immune-related adverse events after anti-PD1/PDL1 antibody treatment.
- Once received allogeneic organ transplantation (including bone marrow transplantation and peripheral stem cell transplantation, except for corneal transplantation);
- Have clinical symptoms of central nervous system metastases;
- Have used a large number of glucocorticoids or other immunosuppressive agents within 4 weeks;
- Have any active autoimmune disease ;
- Be in active infection or undergo an unknown cause fever> 38.5 ℃ during screening or before the first administration(except tumor fever which evaluated by the researchers have no effect to enrollment );
- Received chemotherapy or small molecule targeted drug therapy in 4 weeks prior to chemotherapy pretreatment;
- Received any antibody drug therapy (including PD-1 and CTLA-4) within 6 weeks before the treatment period;
- Severe liver and kidney dysfunction or uncontrollable diabetes, hypertension and other chronic systemic diseases; severe coagulation disorders, mental illness, cardiopulmonary disease,hydrothorax or ascites;
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental
Arm Description
Drug:Cyclophosphamide Biological/Vaccine:Tumor Specific Antigen-loaded Dendritic Cells
Outcomes
Primary Outcome Measures
safety endpoint
All the local or systemic reactions, adverse events and serious adverse events that occurred between the first and the second TSA-DC administration.
Overall Response Rate
Percentage of cases whose tumor shrinks to a certain extent and remains for a certain period of time.
Proportion of the number of cases that has produced tumor-specific antigen-specific T cells in peripheral blood.
Secondary Outcome Measures
Secondary safety endpoint
All local or systemic reactions, adverse events and serious adverse events that occurred from entering the trial until 30 days after the last treatment;
Six month DCR(CRR+PRR+SDR)
Percentage of cases with no progression (CR + PR + SD) in 6 months after initiation of treatment;
Duration of Response(DOR)
The time from the first tumor evaluation of remission(CR + PR ) till the first assessment of PD or the end the study.
Progression-free survival(PFS)
The time from entering the trial till the subject has been diagnosed with progression of disease or died.
rate of 12-month survival
Percentage of cases with 12 months survival after initiation of treatment in all the subjects;
Quality score of life improvement
Evaluated by the questionnaire of life improvement quality collected from the screening to treatment periods.
Full Information
NCT ID
NCT03185429
First Posted
June 11, 2017
Last Updated
August 11, 2017
Sponsor
BGI, China
Collaborators
Fujian Cancer Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03185429
Brief Title
TSA-DC Vaccine in Treating Patients With Gastrointestinal Solid Tumor
Official Title
Study of DC Vaccine Loaded Tumor Specific Antigen in Treating Patients With Gastrointestinal Solid Tumor
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Unknown status
Study Start Date
December 2017 (Anticipated)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
June 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
BGI, China
Collaborators
Fujian Cancer Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The goal of this study is to learn about the safety and tolerance of autologous TSA-DC cell and evaluate the efficacy and feasibility of the cell therapy compared to the patients' past standard regimen. 20 gastrointestinal solid tumors subjects failed from at least one systemic therapy will be enrolled into the trial and receive a succession of treatment of TSA-DC vaccine.
Detailed Description
20 gastrointestinal solid tumor subjects failed from at least one systemic therapy will be enrolled into the trial .Subjects will be given subcutaneous injection of 5.0x10^6-1.0x10^7 TSA-DC on week 1, 3, 5, 11,17,23,35,47. Before the first cell infusion, the subjects should undergo a non-myeloablative chemotherapy regimen of Cyclophosphamide 300mg/m2 iv. Radiologic tumor assessment will be repeated every 8 weeks during treatment, until time of progression. Treatment will continue until disease progression, intolerance of toxic , withdrawal from the study, study completion, or study termination.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tumor Gastric, Tumor, Colorectal
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Drug:Cyclophosphamide
Biological/Vaccine:Tumor Specific Antigen-loaded Dendritic Cells
Intervention Type
Biological
Intervention Name(s)
Tumor Specific Antigen-loaded Dendritic Cells
Other Intervention Name(s)
TSA-DC vaccine
Intervention Description
Subjects will be given subcutaneous injection of 5.0x10^6-1.0x10^7 TSA-DC on week 1,3,5,11,17,23,35,47.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
300 mg/m2 by vein before the first cell infusion.
Primary Outcome Measure Information:
Title
safety endpoint
Description
All the local or systemic reactions, adverse events and serious adverse events that occurred between the first and the second TSA-DC administration.
Time Frame
one year
Title
Overall Response Rate
Description
Percentage of cases whose tumor shrinks to a certain extent and remains for a certain period of time.
Time Frame
one year
Title
Proportion of the number of cases that has produced tumor-specific antigen-specific T cells in peripheral blood.
Time Frame
one year
Secondary Outcome Measure Information:
Title
Secondary safety endpoint
Description
All local or systemic reactions, adverse events and serious adverse events that occurred from entering the trial until 30 days after the last treatment;
Time Frame
one year
Title
Six month DCR(CRR+PRR+SDR)
Description
Percentage of cases with no progression (CR + PR + SD) in 6 months after initiation of treatment;
Time Frame
6 month
Title
Duration of Response(DOR)
Description
The time from the first tumor evaluation of remission(CR + PR ) till the first assessment of PD or the end the study.
Time Frame
one year
Title
Progression-free survival(PFS)
Description
The time from entering the trial till the subject has been diagnosed with progression of disease or died.
Time Frame
one year
Title
rate of 12-month survival
Description
Percentage of cases with 12 months survival after initiation of treatment in all the subjects;
Time Frame
one year
Title
Quality score of life improvement
Description
Evaluated by the questionnaire of life improvement quality collected from the screening to treatment periods.
Time Frame
one year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Be ≥18 and ≤75,no gender based;
Expression of HLA-A0201/1101/2402;
Histopathologic documentation of gastrointestinal solid tumors(stomach cancer or colorectal cancer ) concurrent with the diagnosis of metastatic disease, and the tumor is Measurable;
Patients must have adequate tissue (fresh or paraffin block) for DNA extraction, which is used for gene sequencing, and prognoses the tumor specific antigen in turn,can predict to have new tumor antigens with high affinity for MHC molecules;
Failure in conventional treatment, or though benefit from chemotherapy the patient can't tolerant subjectively;
Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 and an anticipate life expectancy of at least three months,be cooperate to adverse reactions monitoring and therapeutic evaluation of the treatment;
Participants of child-bearing potential must agree to use adequate contraceptive methods up to 12 months after the pretreatment;
Serology:Seronegative for HIV antibody,seronegative for hepatitis C antibody. Hematology:Absolute neutrophil count ≥ 1000/mm(3) without the support of filgrastim ,WBC ≥ 3000/mm(3),lymphocyte count ≥ 800/mm(3),Platelet count ≥ 100,000/mm(3),Hemoglobin ≥ 9.0 g/dl Chemistry:Serum ALT/AST ≤ 2.5 times the upper limit of normal,Serum Creatinine ≤1.6 mg/dl,Total bilirubin < 1.5 mg/dl, except in patients with Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dl;
Patients or their legal representatives are willing and able to understand and written informed consent form for the trial;
Exclusion Criteria:
Is pregnant or breastfeeding,or expecting to conceive;
Have a history of severe immediate hypersensitivity reaction to any of the agents used in this study.
Suffered grade 3-4 major organ immune-related adverse events after anti-PD1/PDL1 antibody treatment.
Once received allogeneic organ transplantation (including bone marrow transplantation and peripheral stem cell transplantation, except for corneal transplantation);
Have clinical symptoms of central nervous system metastases;
Have used a large number of glucocorticoids or other immunosuppressive agents within 4 weeks;
Have any active autoimmune disease ;
Be in active infection or undergo an unknown cause fever> 38.5 ℃ during screening or before the first administration(except tumor fever which evaluated by the researchers have no effect to enrollment );
Received chemotherapy or small molecule targeted drug therapy in 4 weeks prior to chemotherapy pretreatment;
Received any antibody drug therapy (including PD-1 and CTLA-4) within 6 weeks before the treatment period;
Severe liver and kidney dysfunction or uncontrollable diabetes, hypertension and other chronic systemic diseases; severe coagulation disorders, mental illness, cardiopulmonary disease,hydrothorax or ascites;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yu Chen, Doctor
Phone
13859089836
Email
fannychenling05@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ZengQing Guo, Professor
Organizational Affiliation
Fujian Cancer Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
23838316
Citation
Chiang CL, Kandalaft LE, Tanyi J, Hagemann AR, Motz GT, Svoronos N, Montone K, Mantia-Smaldone GM, Smith L, Nisenbaum HL, Levine BL, Kalos M, Czerniecki BJ, Torigian DA, Powell DJ Jr, Mick R, Coukos G. A dendritic cell vaccine pulsed with autologous hypochlorous acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside. Clin Cancer Res. 2013 Sep 1;19(17):4801-15. doi: 10.1158/1078-0432.CCR-13-1185. Epub 2013 Jul 9.
Results Reference
background
PubMed Identifier
24583792
Citation
Schuler PJ, Harasymczuk M, Visus C, Deleo A, Trivedi S, Lei Y, Argiris A, Gooding W, Butterfield LH, Whiteside TL, Ferris RL. Phase I dendritic cell p53 peptide vaccine for head and neck cancer. Clin Cancer Res. 2014 May 1;20(9):2433-44. doi: 10.1158/1078-0432.CCR-13-2617. Epub 2014 Feb 28.
Results Reference
background
PubMed Identifier
25837513
Citation
Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP. Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science. 2015 May 15;348(6236):803-8. doi: 10.1126/science.aaa3828. Epub 2015 Apr 2.
Results Reference
background
Learn more about this trial
TSA-DC Vaccine in Treating Patients With Gastrointestinal Solid Tumor
We'll reach out to this number within 24 hrs