Clinical Trials List
Protocol NumberDC-CIK_TRIAL_PROPOSAL (CDE編號:108CONS08300.1)
NCT Number(ClinicalTrials.gov Identfier)NCT05020119
2020-06-01 - 2021-05-31
Phase I
Recruiting3
A phase I study to evaluate the safety, tolerability, and antitumor activity of neoantigen-expanded autologous immune cell therapy for solid tumors
-
Sponsor
Chang Gung Memorial Hospital
-
Trial scale
Taiwan Multiple Center
-
Update
2023/03/10
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- Cheng-Ta Yang Division of Thoracic Medicine
- Chan-Keng Yang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- Chun-Bing Chen Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Hung-Chih Hsu Division of Hematology & Oncology
- See-Tong Pang Division of Urology
- Wen-Hung Chung Division of Dermatology
- 洪舜郁 Division of Hematology & Oncology
- Yung-Chang Lin Division of Hematology & Oncology
- Chyong-Huey Lai Division of Obstetrics & Gynecology
- Kuo-Chen Wei Division of Orthopedics
- 邱志勇 Division of Pediatrics
- Yun-Hsin Tang Division of Obstetrics & Gynecology
- Wen-Cheng Chang Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Chun-Yen Lin Digestive System Department
- Chun-Nan Yeh Division of Gastroenterological Surgery
- Hung-Ming Wang Division of Hematology & Oncology
- Wen-Chi Chou Division of Hematology & Oncology
- Chih-Liang Wang Division of Thoracic Medicine
- 吳吉妮 Division of Dermatology
- Chun-Bing Chen Division of Dermatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Solid Tumor
Objectives
Primary Objective:
To evaluate the feasibility and safety of neoantigen-expanded autologous immune cell
therapy for patients with solid tumor.
Secondary Objective:
To evaluate the antitumor activity of neoantigen-expanded autologous immune cell
therapy for patients with solid tumor.
Test Drug
Neoantigen-expanded autologous immune cell
Active Ingredient
Dendritic cells-cytokine induced killer cells
Dosage Form
細胞數/200-400 毫升 [(1±30%)×109cells /200毫升，(5±30%)×109cells /200毫升，(1±30%)×1010cells/400毫升]
Dosage
(1±30%)x109cells，(5±30%)x109cells，(1±30%)x1010cells
Endpoints
1. Primary endpoint(s):
Acute and subacute toxicities and AEs [ Time Frame: baseline to 20 weeks after infusion ]
To determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT) of
neoantigen-expanded autologous immune cell therapy.
To calculate the incidence of ≥ grade 3 immune related Adverse Events (irAEs) related to cell
infusion.
Adverse effects (AEs) and in particular cytokine release syndrome (CRS) and potential
autoimmune AEs will be monitored.
2. Secondary endpoints:
To evaluate the antitumor activity of neoantigen-expanded autologous immune cell therapy for
patients with solid tumor.
Acute and subacute toxicities and AEs [ Time Frame: baseline to 20 weeks after infusion ]
To determine the Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT) of
neoantigen-expanded autologous immune cell therapy.
To calculate the incidence of ≥ grade 3 immune related Adverse Events (irAEs) related to cell
infusion.
Adverse effects (AEs) and in particular cytokine release syndrome (CRS) and potential
autoimmune AEs will be monitored.
2. Secondary endpoints:
To evaluate the antitumor activity of neoantigen-expanded autologous immune cell therapy for
patients with solid tumor.
Inclution Criteria
Main inclusion criteria:
1. Solid tumors, including colorectal cancer, gastric cancer, pancreatic cancer, esophageal cancer,
liver cancer, gastrointestinal stromal tumor, biliary tract cancer, kidney cancer, bladder cancer,
prostate cancer, Head and neck cancer, nasopharyngeal cancer, skin cancer, melanoma,
malignant sarcoma, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, lung
cancer, and brain cancer.
2. The patient has at least one lesion that can be obtained by sectioning or cutting to identify
somatic mutations from the tumor.
3. The patient belongs to stage IV solid tumor, or refractory stage I-III solid tumor to approved
standard systemic therapy; and is willing to be an adjuvant treatment after standard treatment, or
is not suitable for standard treatment, or cannot accept standard treatment, and needs more
effective treatment.
When evaluating to participate in the trial, patient's body still has solid tumor.
The invalid definition of standard treatment is as follows:
a. Colorectal cancer patients must have received at least two prior chemotherapies, including
oxaliplatin and irinotecan; or at least one of the target therapies for colorectal cancer,
including Cetuximab, Bevacizumab, Panitumumab, etc. After that, patient’s tumor still
recurs and cannot be surgically removed.
b. Patients with gastric cancer and pancreatic cancer must undergo eradication surgery or have
received chemotherapies. After that, patient’s tumor still recurs and cannot be surgically
removed.
c. Patients with esophageal cancer must have received second-line systemic drug therapy (eg.
chemotherapies or immunotherapies)
d. Patients with liver cancer must undergo surgery; radiofrequency ablation, or transcatheterial
chemoembolization. After that, patient’s tumor still recurs and cannot be surgically removed.
e. Patients with biliary tract cancer must refractory to first line treatment contained with
gemcitabine
f. Patients with gastrointestinal stromal tumors must have received more than first line of target
treatment. After that, patient’s tumor still recurs and cannot be surgically removed.
g. Patients with renal cancer must have received 2nd-line tretaments (including chemotherapies
or target therapies or combined with immunotherapies. After that, patient’s tumor still recurs
and cannot be surgically removed.
h. Patients with bladder cancer must have received platinum-based chemotherapy or unable to
receive chemotherapies, have received immunomedical therapy. After that, patient’s tumor
still recurs and cannot be surgically removed.
i. Patients with prostate cancer must develop biochemical failure and continue to disease
progression after receiving chemotherapies or second-line hormone therapies.
j. Patients with head and neck cancer and nasopharyngeal carcinoma must have received
chemotherapies, imcluding cetuximab or platinum. After that, patient’s tumor still recurs and
cannot be surgically removed.
k. Patients with skin cancer and melanoma must have received at least one systemic treatment.
If there is a genetic mutation for enrolled patients, patients must be refractory to target
therapies (related to mutation) or to first-line chemotherapies.
l. Patients with malignant sarcoma must have received first-line chemotherapies or target
therapies. After that, patient’s tumor still recurs and cannot be surgically removed.
m. Patients with breast cancer who are unable to undergo surgery must have received
anthracycline taxsnes and any third-line medication. If the patient with a positive ER gene, at
least three third-line hormone therapies should be used. If patient with a positive HER2 gene,
at least Hercrptin and Perjecta or T-DM1 should be used.
n. Ovarian cancer patients must have received platinum-containing (platinum) chemotherapies
to stop recurrence within 1-6 months; or have done more than 2nd-line of chemotherapies.
After that, patient’s tumor still recurs
o. Patients with cervical cancer must have received radiation therapy and chemotherapies. After
that, patient’s tumor still recurs and cannot be surgically removed.
p. Patients with endometrial cancer must have received hormone therapy after relapse; disease
is deteriorated during chemotherapies; or patient’s tumor still recurs after radiotherapy.
q. Patients with lung cancer must be refractory to first line standard treatment contained with
platinum-based doublet chemotherapy in the patients without detected driver mutation or
those patients have failed to tyrosine kinase inhibitors and standard platinum-based doublet chemotherapy in those with druggable driver mutation.
r. Patients with brain cancer must have received radiation therapy and chemotherapies; or
patient’s tumor still recurs within one to six months after chemotherapies, and can not be
completely resected; or patients have failed to receive target therapies.
4. Patients who are willing to receive cell therapy.
5. Age is greater than or equal to 18 years old.
6. Clinical performance status of ECOG 0 or 1.
7. Life expectancy exceeds four months
8. Patients can take foods and drugs orally.
9. Hematology:
a. Absolute neutrophil count greater than 1000/mm3
without support of filgrastim
b. Normal WBC (> 3000/mm3
).
c. Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this cut-off.
d. Platelet count greater than 100,000/mm3
e. Normal prothrombin time (less than or equal to 15.2 seconds)
10. The heart, lung and liver function of the patient must comply with:
a. NYHA (the New York Heart Association) Functional Class I or I
b. Serum ALT / AST is less than 250 U/L (this condition can be exempted for patients with
advanced hepatocellular carcinoma)
c. Serum creatinine less than or equal to 1.6 mg/dl.
d. Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert’s Syndrome, who
must have a total bilirubin less than or equal to 3 mg/dl.
e. eGFR is greater than 60mL/min/1.73m2
(this condition can be exempted for patients with
advanced renal cell carcinoma)
11. Patient with primary major surgery needs to have elapsed ≥ 4 weeks prior to the planned first
study treatment day.
12. Patient who has ever received chemotherapy, radiotherapy or immunotherapy (anti-CTLA4 or
anti-PD1/PDL1), or biologic therapy (anti-VEGF or anti-TKR) modalities need to wash-out ≥
4 weeks prior to the baseline visit.
13.Stop receiving systemic immunosuppressive drugs within 7 days before starting the immune
cell infusion
14. Willing to practice birth control during treatment
15. Able to understand and sign the Informed Consent form
1. Solid tumors, including colorectal cancer, gastric cancer, pancreatic cancer, esophageal cancer,
liver cancer, gastrointestinal stromal tumor, biliary tract cancer, kidney cancer, bladder cancer,
prostate cancer, Head and neck cancer, nasopharyngeal cancer, skin cancer, melanoma,
malignant sarcoma, breast cancer, ovarian cancer, cervical cancer, endometrial cancer, lung
cancer, and brain cancer.
2. The patient has at least one lesion that can be obtained by sectioning or cutting to identify
somatic mutations from the tumor.
3. The patient belongs to stage IV solid tumor, or refractory stage I-III solid tumor to approved
standard systemic therapy; and is willing to be an adjuvant treatment after standard treatment, or
is not suitable for standard treatment, or cannot accept standard treatment, and needs more
effective treatment.
When evaluating to participate in the trial, patient's body still has solid tumor.
The invalid definition of standard treatment is as follows:
a. Colorectal cancer patients must have received at least two prior chemotherapies, including
oxaliplatin and irinotecan; or at least one of the target therapies for colorectal cancer,
including Cetuximab, Bevacizumab, Panitumumab, etc. After that, patient’s tumor still
recurs and cannot be surgically removed.
b. Patients with gastric cancer and pancreatic cancer must undergo eradication surgery or have
received chemotherapies. After that, patient’s tumor still recurs and cannot be surgically
removed.
c. Patients with esophageal cancer must have received second-line systemic drug therapy (eg.
chemotherapies or immunotherapies)
d. Patients with liver cancer must undergo surgery; radiofrequency ablation, or transcatheterial
chemoembolization. After that, patient’s tumor still recurs and cannot be surgically removed.
e. Patients with biliary tract cancer must refractory to first line treatment contained with
gemcitabine
f. Patients with gastrointestinal stromal tumors must have received more than first line of target
treatment. After that, patient’s tumor still recurs and cannot be surgically removed.
g. Patients with renal cancer must have received 2nd-line tretaments (including chemotherapies
or target therapies or combined with immunotherapies. After that, patient’s tumor still recurs
and cannot be surgically removed.
h. Patients with bladder cancer must have received platinum-based chemotherapy or unable to
receive chemotherapies, have received immunomedical therapy. After that, patient’s tumor
still recurs and cannot be surgically removed.
i. Patients with prostate cancer must develop biochemical failure and continue to disease
progression after receiving chemotherapies or second-line hormone therapies.
j. Patients with head and neck cancer and nasopharyngeal carcinoma must have received
chemotherapies, imcluding cetuximab or platinum. After that, patient’s tumor still recurs and
cannot be surgically removed.
k. Patients with skin cancer and melanoma must have received at least one systemic treatment.
If there is a genetic mutation for enrolled patients, patients must be refractory to target
therapies (related to mutation) or to first-line chemotherapies.
l. Patients with malignant sarcoma must have received first-line chemotherapies or target
therapies. After that, patient’s tumor still recurs and cannot be surgically removed.
m. Patients with breast cancer who are unable to undergo surgery must have received
anthracycline taxsnes and any third-line medication. If the patient with a positive ER gene, at
least three third-line hormone therapies should be used. If patient with a positive HER2 gene,
at least Hercrptin and Perjecta or T-DM1 should be used.
n. Ovarian cancer patients must have received platinum-containing (platinum) chemotherapies
to stop recurrence within 1-6 months; or have done more than 2nd-line of chemotherapies.
After that, patient’s tumor still recurs
o. Patients with cervical cancer must have received radiation therapy and chemotherapies. After
that, patient’s tumor still recurs and cannot be surgically removed.
p. Patients with endometrial cancer must have received hormone therapy after relapse; disease
is deteriorated during chemotherapies; or patient’s tumor still recurs after radiotherapy.
q. Patients with lung cancer must be refractory to first line standard treatment contained with
platinum-based doublet chemotherapy in the patients without detected driver mutation or
those patients have failed to tyrosine kinase inhibitors and standard platinum-based doublet chemotherapy in those with druggable driver mutation.
r. Patients with brain cancer must have received radiation therapy and chemotherapies; or
patient’s tumor still recurs within one to six months after chemotherapies, and can not be
completely resected; or patients have failed to receive target therapies.
4. Patients who are willing to receive cell therapy.
5. Age is greater than or equal to 18 years old.
6. Clinical performance status of ECOG 0 or 1.
7. Life expectancy exceeds four months
8. Patients can take foods and drugs orally.
9. Hematology:
a. Absolute neutrophil count greater than 1000/mm3
without support of filgrastim
b. Normal WBC (> 3000/mm3
).
c. Hemoglobin greater than 8.0 g/dl. Subjects may be transfused to reach this cut-off.
d. Platelet count greater than 100,000/mm3
e. Normal prothrombin time (less than or equal to 15.2 seconds)
10. The heart, lung and liver function of the patient must comply with:
a. NYHA (the New York Heart Association) Functional Class I or I
b. Serum ALT / AST is less than 250 U/L (this condition can be exempted for patients with
advanced hepatocellular carcinoma)
c. Serum creatinine less than or equal to 1.6 mg/dl.
d. Total bilirubin less than or equal to 2 mg/dl, except in patients with Gilbert’s Syndrome, who
must have a total bilirubin less than or equal to 3 mg/dl.
e. eGFR is greater than 60mL/min/1.73m2
(this condition can be exempted for patients with
advanced renal cell carcinoma)
11. Patient with primary major surgery needs to have elapsed ≥ 4 weeks prior to the planned first
study treatment day.
12. Patient who has ever received chemotherapy, radiotherapy or immunotherapy (anti-CTLA4 or
anti-PD1/PDL1), or biologic therapy (anti-VEGF or anti-TKR) modalities need to wash-out ≥
4 weeks prior to the baseline visit.
13.Stop receiving systemic immunosuppressive drugs within 7 days before starting the immune
cell infusion
14. Willing to practice birth control during treatment
15. Able to understand and sign the Informed Consent form
Exclusion Criteria
Main exclusion criteria:
1.Women of child-bearing potential who are pregnant or breastfeeding because of the potentially
dangerous effects of the treatment on the fetus or infant.
2. A systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders,
cardiovascular disease, respiratory disease, immune system disease, myocardial infarction,
cardiac arrhythmia, obstructive or restrictive pulmonary disease.
3. Active tuberculosis (a history of tuberculosis exposure or a positive test for tuberculosis,
inlcuding clinical, physical or imaging evidence).
4. Acute or chronic infectious diseases (including: syphilis or human T lymphoblast infection)
(in this trial, patients with HIV, HTLV, or syphilis infection are also excluded. HIV-positive patients may have lower immunity, resulting in lower response to treatment or the toxicity after
treatment is more sensitive)
5. Biliary or intestinal occlusion, cholangitis or severe gastrointestinal bleeding
6. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease
[SCID] and acquired immune deficiency syndrome [AIDS]).
7. ≥ grade 4 major organ immune-related Adverse Events (irAEs) following treatment with
immune checkpoint inhibitors.
8. History of coronary revascularization or ischemic symptoms
9. Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested in
patients with:
a. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial
fibrillation, ventricular tachycardia, second or third degree heart block
b. Age ≥ 60 years old
10. A rapidly deteriorating disease that the trial investigators believes may not be able to tolerate
treatment or testing procedures
1.Women of child-bearing potential who are pregnant or breastfeeding because of the potentially
dangerous effects of the treatment on the fetus or infant.
2. A systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders,
cardiovascular disease, respiratory disease, immune system disease, myocardial infarction,
cardiac arrhythmia, obstructive or restrictive pulmonary disease.
3. Active tuberculosis (a history of tuberculosis exposure or a positive test for tuberculosis,
inlcuding clinical, physical or imaging evidence).
4. Acute or chronic infectious diseases (including: syphilis or human T lymphoblast infection)
(in this trial, patients with HIV, HTLV, or syphilis infection are also excluded. HIV-positive patients may have lower immunity, resulting in lower response to treatment or the toxicity after
treatment is more sensitive)
5. Biliary or intestinal occlusion, cholangitis or severe gastrointestinal bleeding
6. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease
[SCID] and acquired immune deficiency syndrome [AIDS]).
7. ≥ grade 4 major organ immune-related Adverse Events (irAEs) following treatment with
immune checkpoint inhibitors.
8. History of coronary revascularization or ischemic symptoms
9. Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested in
patients with:
a. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial
fibrillation, ventricular tachycardia, second or third degree heart block
b. Age ≥ 60 years old
10. A rapidly deteriorating disease that the trial investigators believes may not be able to tolerate
treatment or testing procedures
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
25 participants
