TSA-DC Vaccine in Treating Patients With Gastrointestinal Solid Tumor

Tumor Gastric Clinical Trial

Official title:

Study of DC Vaccine Loaded Tumor Specific Antigen in Treating Patients With Gastrointestinal Solid Tumor

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03185429
• Other study ID #: BGI-002
• Status: Not yet recruiting
• Phase: N/A
• First received: June 11, 2017
• Last updated: August 11, 2017
• Start date: December 2017
• Est. completion date: June 2019

Study information

• Verified date: August 2017
• Source: BGI, China
• Contact: Yu Chen, Doctor
• Phone: 13859089836
• Email: fannychenling05[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: June 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Neoplasms
• Stomach Neoplasms
• Tumor Gastric
• Tumor, Colorectal

Intervention

Biological:
• Tumor Specific Antigen-loaded Dendritic Cells
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.

Drug:
• Cyclophosphamide
300 mg/m2 by vein before the first cell infusion.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
BGI, China	Fujian Cancer Hospital

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	one year
Primary	Overall Response Rate	Percentage of cases whose tumor shrinks to a certain extent and remains for a certain period of time.	one year
Primary	Proportion of the number of cases that has produced tumor-specific antigen-specific T cells in peripheral blood.		one year
Secondary	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;	one year
Secondary	Six month DCR(CRR+PRR+SDR)	Percentage of cases with no progression (CR + PR + SD) in 6 months after initiation of treatment;	6 month
Secondary	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.	one year
Secondary	Progression-free survival(PFS)	The time from entering the trial till the subject has been diagnosed with progression of disease or died.	one year
Secondary	rate of 12-month survival	Percentage of cases with 12 months survival after initiation of treatment in all the subjects;	one year
Secondary	Quality score of life improvement	Evaluated by the questionnaire of life improvement quality collected from the screening to treatment periods.	one year