Clinical trial NCT03185429: 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
Overall status: UNKNOWN
Phase: NA
Conditions: Tumor Gastric
Tumor, Colorectal
Lead sponsor: BGI, China
Sponsor class: OTHER
Collaborators: name: Fujian Cancer Hospital
First posted: 2017-06-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Be ≥18 and ≤75,no gender based;
2. Expression of HLA-A0201/1101/2402;
3. Histopathologic documentation of gastrointestinal solid tumors(stomach cancer or colorectal cancer ) concurrent with the diagnosis of metastatic disease, and the tumor is Measurable;
4. 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;
5. Failure in conventional treatment， or though benefit from chemotherapy the patient can't tolerant subjectively;
6. 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;
7. Participants of child-bearing potential must agree to use adequate contraceptive methods up to 12 months after the pretreatment;
8. 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;
9. Patients or their legal representatives are willing and able to understand and written informed consent form for the trial;

Exclusion Criteria:

1. Is pregnant or breastfeeding,or expecting to conceive;
2. Have a history of severe immediate hypersensitivity reaction to any of the agents used in this study.
3. Suffered grade 3-4 major organ immune-related adverse events after anti-PD1/PDL1 antibody treatment.
4. Once received allogeneic organ transplantation (including bone marrow transplantation and peripheral stem cell transplantation, except for corneal transplantation);
5. Have clinical symptoms of central nervous system metastases;
6. Have used a large number of glucocorticoids or other immunosuppressive agents within 4 weeks;
7. Have any active autoimmune disease ;
8. 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 );
9. Received chemotherapy or small molecule targeted drug therapy in 4 weeks prior to chemotherapy pretreatment;
10. Received any antibody drug therapy (including PD-1 and CTLA-4) within 6 weeks before the treatment period;
11. Severe liver and kidney dysfunction or uncontrollable diabetes, hypertension and other chronic systemic diseases; severe coagulation disorders, mental illness, cardiopulmonary disease，hydrothorax or ascites;

Primary outcomes:
measure: safety endpoint
timeFrame: one year
measure: Overall Response Rate
timeFrame: one year
measure: Proportion of the number of cases that has produced tumor-specific antigen-specific T cells in peripheral blood.
timeFrame: one year
Secondary outcomes:
measure: Secondary safety endpoint
timeFrame: one year
measure: Six month DCR(CRR+PRR+SDR)
timeFrame: 6 month
measure: Duration of Response(DOR)
timeFrame: one year
measure: Progression-free survival(PFS)
timeFrame: one year
measure: rate of 12-month survival
timeFrame: one year
measure: Quality score of life improvement
timeFrame: one year
Other outcomes:
Locations:
Study officials:
affiliation: Fujian Cancer Hospital
name: ZengQing Guo, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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