TSA-DC Vaccine in Treating Patients With Gastrointestinal Solid Tumor

Not Applicable

• Conditions: Tumor, Colorectal; Tumor Gastric
• Interventions: Biological: Tumor Specific Antigen-loaded Dendritic Cells; Drug: Cyclophosphamide

• Registration Number: NCT03185429
• Lead Sponsor: BGI, China

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.

Study Timeline

• Study First Submitted: 2017-06-11
• Study First Submitted QC: 2017-06-12
• Study First Posted: 2017-06-14
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-11
• Last Update Posted: 2017-08-14
• Study Start: 2017-12
• Primary Completion: 2018-12
• Study Completion: 2019-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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;

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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;

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Tumor Specific Antigen-loaded Dendritic Cells	Drug:Cyclophosphamide Biological/Vaccine:Tumor Specific Antigen-loaded Dendritic Cells
Experimental	Cyclophosphamide	Drug:Cyclophosphamide Biological/Vaccine:Tumor Specific Antigen-loaded Dendritic Cells

Primary Outcome Measures

Name	Time	Method
safety endpoint	one year	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	one year	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.	one year

Secondary Outcome Measures

Name	Time	Method
Secondary safety endpoint	one year	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)	6 month	Percentage of cases with no progression (CR + PR + SD) in 6 months after initiation of treatment;
Duration of Response(DOR)	one year	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)	one year	The time from entering the trial till the subject has been diagnosed with progression of disease or died.
rate of 12-month survival	one year	Percentage of cases with 12 months survival after initiation of treatment in all the subjects;
Quality score of life improvement	one year	Evaluated by the questionnaire of life improvement quality collected from the screening to treatment periods.