Pancreatic Ductal AdenocarcinomaPhase 2/3NCT05955157
Combined S-1 With DC+CIK As Maintenance Therapy For Advanced Pancreatic Ductal Adenocarcinoma
A Phase 2/3 study testing Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapy and Tegafur Only Product in people with Pancreatic Ductal Adenocarcinoma and Advanced Solid Tumor, run by University of Malaya at 1 site in Malaysia.
Trial summary
The goal of this randomized phase 2 controlled clinical trial is to study safety, efficacy of S-1 combined DC+CIK maintenance therapy compared with S-1 alone in improving clinical benefit rate (CBR) among advanced PDAC patients. The main objectives aim to be achieved through this study are : 1. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pancreatic Ductal Adenocarcinoma, Advanced Solid Tumor
- What is being tested?
- Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapy and Tegafur Only Product
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 1 siteMalaysia
- Study dates
- 3 Jan 2023to Jun 2025
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically and cytologically confirmed advanced pancreatic ductal adenocarcinoma according to AJCC (American Joint Committee on Cancer) TNM system;
- Have undergone first-line of chemotherapy (modified FOLFIRINOX or gemcitabine-based) for at least 3 months and achieved at least stable disease;
- Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2;
- Age above 18 ages
- Life expectancy more than three months.
Who cannot join
- Pregnant and lactating women
- Concomitant beta-adrenergic drug blockers medication
- Active infection
- Current enrollment in another clinical study with an investigational agent
- Patients who undergo radiotherapy to pancreas or metastatic site need to be recovered from the toxicities
Trial locations and contacts
1 site in 1 country.
Malaysia1 site, 1 recruiting
- Recruiting
Clinical Oncology Department, Ummc
Petaling Jaya, Kuala Lumpur, 59100
HO GWO FUANG, 03-79492120, gwoho@um.edu.my
THIAN QIN ZHANG, 03-79492120, elson_thian92@hotmail.com
About this study
Official title: Phase II Randomized Controlled Trial Of Dendritic Cell + Cytokine-Induced Killer Cell Immunotherapy With S-1 Versus S-1 Alone As Maintenance Therapy For Advanced Pancreatic Ductal Adenocarcinoma Patients
The goal of this randomized phase 2 controlled clinical trial is to study safety, efficacy of S-1 combined DC+CIK maintenance therapy compared with S-1 alone in improving clinical benefit rate (CBR) among advanced PDAC patients. The main objectives aim to be achieved through this study are :
- To evaluate the safety of DC+CIK combined immunotherapy when administered with the chemotherapy S-1 as maintenance therapy following first-line chemotherapy regime to advanced pancreatic ductal adenocarcinoma patients.
- To demonstrate the superiority of of DC+CIK combined immunotherapy in improving clinical benefit rate (CBR) of advanced pancreatic ductal adenocarcinoma patients when administered with the chemotherapy S-1 as maintenance therapy following first-line chemotherapy regime.
- To investigate the ability of S-1 combined DC+CIK maintenance therapy in reducing pancreatic ductal adenocarcinoma patients' circulating cancer stem cells (CSCs).
Read more
In this study, subjects who achieve at least stable disease or partial response will be randomized in ratio of 1:1 into treatment group: DC-CIK plus S1 (27 patients) and control group: S-1 alone (27 patients). For treatment group, they will be infused with DC first, followed by CIK immune cells on day 1. DC+CIK immunotherapy will be repeated for another 2 times (day 8 and 15) as one cycle. All patients are left to rest for a week (start from day 21) prior to receive another 3 times of infusion (day 28, 35 and 42) if condition allowed. Additional third cycle can be performed on those who tolerate well with no toxicity or respond very well. Patients from treatment group will be assessed for their eligibility to receive booster dose on following conditions: 1) tumour achieves partial response or stable disease and 2) ECOG-PS performance status of 0-2 and 3) doesn't exhibit grade 1 and 2 toxicities to improve tumour control.
Additionally, S-1 will be given twice daily after meals for 2 weeks as first cycle along with DC+CIK. Next second cycle of S-1 will be given after 7-days (1 week) rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent. Dose of S-1 will be determined according to the body surface area.
Meanwhile, patients from control group will receive S-1 alone as maintenance therapy twice daily after meals for 14 days (2 weeks) as one cycle. The next cycle of S-1 will be given after 7-days rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent.
Read the detailed description
This trial is designed as randomized phase 2 controlled clinical trial.
Subjects who fulfill following inclusion criteria will be admitted to this phase 2 trial and will be excluded if they fulfill any one of the exclusion criteria. All patients must have undergone first-line of chemotherapy (either modified FOLFIRINOX or gemcitabine-based) for at least 3 months and achieved at least stable disease. The inclusion criteria are as follow: 1) histologically and cytologically confirmed advanced pancreatic ductal adenocarcinoma according to AJCC (American Joint Committee on Cancer) TNM system; 2) have undergone first-line of chemotherapy (modified FOLFIRINOX or gemcitabine-based) for at least 3 months and achieved at least stable disease; 3) Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2; 4) age above 18 ages and 5) life expectancy more than three months. Meanwhile, the exclusion criteria are 1) pregnant and lactating women; 2) concomitant beta-adrenergic drug blockers medication; 3) active infection; 4) current enrollment in another clinical study with an investigational agent and 5) patients who undergo pancreas or metastatic site radiotherapy need to be recovered from the toxicities.
Next, patients who achieve at least stable disease will be checked for peripheral blood mononuclear cells (PBMC) adequacy, hematoprofiling using full blood count (FBC) and their baseline status. This is followed by leukapheresis once all conditions satisfied and met. Apheretic products will be sent to local sponsor-contracted laboratory prior for incubation of patients' immune cells with PDAC antigens under specific medium.
All subjects in this trial have been diagnosed with advanced stage of PDAC and being treated with standard chemo: modified FOLFIRINOX or gemcitabine-based regime for at least 3 months. Once the DC+CIK infusion bags are ready to be manufactured, those who achieve at least stable disease or partial response will be randomized in ratio of 1:1 into treatment group: DC-CIK plus S1 (27 patients) and control group: S-1 alone (27 patients).
For treatment group, DC+CIK infusion bag will be administrated right after 17 days patients discharged. Patients will be infused with DC first, followed by CIK immune cells on day 1. DC+CIK immunotherapy will be repeated for another 2 times (day 8 and 15) as one cycle. All patients are left to rest for a week (start from day 21) prior to receive another 3 times of infusion (day 28, 35 and 42) if condition allowed. DC+CIK immunotherapy will be offered as two cycles for every patient in treatment group.
Additional third cycle can be performed on those who tolerate well with no toxicity or respond very well. Patients from treatment group will be assessed for their eligibility to receive booster dose on following conditions: 1) tumour achieves partial response or stable disease and 2) ECOG-PS performance status of 0-2 and 3) doesn't exhibit grade 1 and 2 toxicities to improve tumour control.
Additionally, S-1 will be given twice daily after meals for 2 weeks as first cycle along with DC+CIK. Next second cycle of S-1 will be given after 7-days (1 week) rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent. Dose of S-1 will be determined according to the body surface area.
Meanwhile, patients from control group will receive S-1 alone as maintenance therapy twice daily after meals for 14 days (2 weeks) as one cycle. The next cycle of S-1 will be given after 7-days rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent.
All patients will be followed up for clinical effects of S-1 combined maintenance therapy translated by tumour best overall response towards the treatment, either complete response (CR), partial response (PR), stable disease (SD) outcomes or progression disease (PD) and level of prognostic biomarkers. Besides, all patients will undergo baseline CT/MRI scan within 4 weeks of patient randomization and before immunotherapy being initiated. This is followed by reassessment CT/MRI scan at the end of 8th weeks starting from date of first treatment, and after S-1 combined DC+CIK immunotherapy completed. All patients will be followed-up regularly to monitor disease progression using reassessment CT/MRI scan at eight weeks interval until first PD observed (Timeframe = 12 months).
Patients' blood will be taken before maintenance treatment initiated and after maintenance treatment completed to evaluate serum cytokine concentration changes and level of circulating cancer stem cells (CSCs). Furthermore, blood will also be taken after each cycle of DC+CIK immunotherapy completed to evaluate baseline peripheral immune profile. Serum CA19-9 concentrations will be monitored every 4 weeks using blood test after first cycle of DC+CIK treatment completed.
Two endoscopic-ultrasound (EUS) guided biopsy pancreatic specimens (optional) will be collected from treatment group patients before maintenance treatment given and after completion of second cycle DC+CIK immunotherapy to quantify tumour-infiltrating lymphocytes (TILs), apoptotic protein expressed on tumour cells and apoptotic cells.
Finally, patients will be monitored for side effects, toxicities and response toward treatment weekly starting on day 7th onward after initial DC+CIK administration. All dated events occurring any time after informed consent will be obtained until 7 days (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.
- Being tested
- Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapy, Tegafur Only Product
- Keywords
- Cell-based Immunotherapy, S-1 combined DC+CIK maintenance treatment, DC+CIK immunotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapyBiological
DC+CIK immunotherapy will be administrated with S-1 chemo drug as maintenance treatment for patients with advanced PDAC
Tegafur Only ProductDrug
Tegafur (TS-1) will be administrated alone as maintenance treatment to control group as standard of care
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | Receiving DC-CIK plus S1 maintenance treatment Receives: Biological: Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapy; Drug: Tegafur Only Product |
| Control Group | Active comparator | Receiving S-1 maintenance treatment alone Receives: Drug: Tegafur Only Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events
Safety of patients towards treatment will be evaluated based on number of adverse events (AEs) and serious adverse events (SAEs) reported.
Measured: 3 months
Incidence of treatment-emergent hematologic side effects
Feasibility of experimental treatment will be evaluated based on result of differential complete blood count.
Measured: 3 months
Secondary outcomes (2)
Clinical benefit rate (CBR) - Change from baseline in tumour burden
Tumour best overall response will be evaluated based on baseline CT/MRI scan, conducted within 4 weeks of patient randomizations and before immunotherapy, followed by reassessment CT/MRI scan at the end of 8th weeks after S-1 combined DC+CIK maintenance therapy completed for both treatment and control group using RECIST Guidelines version 1.1
Measured: 12 months
Efficacy of S-1 combined DC+CIK in controlling tumour
Intratumour analysis of tumour-infiltrating lymphocytes
EUS-biopsy will be consented toward subjects before enroll the trial. Overall, two endoscopic-ultrasound (EUS) guided biopsy pancreatic specimens (optional) will be collected from treatment group patients before maintenance treatment given and after completion of second cycle DC+CIK immunotherapy. The TILs will be stained using immunohistochemistry method before quantified using H-score under bright-field microscope.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2023
- Study start3 Jan 2023
- Primary completionDec 2024 (estimated)
- Study completionJun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Pancreatic Ductal AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by University of MalayaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 52 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Malaya
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05955157
- Sponsor's protocol ID
- DECIMATE 3.0
- Status last verified
- Jan 2023
- First submitted
- 26 Dec 2022
- Last updated
- 10 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bear AS, Vonderheide RH, O'Hara MH. Challenges and Opportunities for Pancreatic Cancer Immunotherapy. Cancer Cell. 2020 Dec 14;38(6):788-802. doi: 10.1016/j.ccell.2020.08.004. Epub 2020 Sep 17.
PubMed 32946773Chen L, Zhang X. Primary analysis for clinical efficacy of immunotherapy in patients with pancreatic cancer. Immunotherapy. 2016 Feb;8(2):223-34. doi: 10.2217/imt.15.105. Epub 2015 Nov 13.
PubMed 26565954Du H, Yang J, Zhang Y. Cytokine-induced killer cell/dendritic cell combined with cytokine-induced killer cell immunotherapy for treating advanced gastrointestinal cancer. BMC Cancer. 2020 Apr 28;20(1):357. doi: 10.1186/s12885-020-06860-y.
PubMed 32345239Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774Foley K, Kim V, Jaffee E, Zheng L. Current progress in immunotherapy for pancreatic cancer. Cancer Lett. 2016 Oct 10;381(1):244-51. doi: 10.1016/j.canlet.2015.12.020. Epub 2015 Dec 23.
PubMed 26723878Gammaitoni L, Giraudo L, Leuci V, Todorovic M, Mesiano G, Picciotto F, Pisacane A, Zaccagna A, Volpe MG, Gallo S, Caravelli D, Giacone E, Venesio T, Balsamo A, Pignochino Y, Grignani G, Carnevale-Schianca F, Aglietta M, Sangiolo D. Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features. Clin Cancer Res. 2013 Aug 15;19(16):4347-58. doi: 10.1158/1078-0432.CCR-13-0061. Epub 2013 Jun 21.
PubMed 23794732Haag GM, Stocker G, Quidde J, Jaeger D, Lordick F. Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer - the multinational MATEO study. BMC Cancer. 2017 Jul 31;17(1):509. doi: 10.1186/s12885-017-3497-9.
PubMed 28760152He W, Huang Z, Zhou S, Huang L, Wang B, Zhu L, Ding Y, Yu YL, Zhang S. The effect of DC+CIK combined therapy on rat liver cancer model and its modulatory effect on immune functions. Eur Rev Med Pharmacol Sci. 2018 Feb;22(3):778-785. doi: 10.26355/eurrev_201802_14312.
PubMed 29461610Miller KD, Fidler-Benaoudia M, Keegan TH, Hipp HS, Jemal A, Siegel RL. Cancer statistics for adolescents and young adults, 2020. CA Cancer J Clin. 2020 Nov;70(6):443-459. doi: 10.3322/caac.21637. Epub 2020 Sep 17.
PubMed 32940362Pan CC, Huang ZL, Li W, Zhao M, Zhou QM, Xia JC, Wu PH. Serum alpha-fetoprotein measurement in predicting clinical outcome related to autologous cytokine-induced killer cells in patients with hepatocellular carcinoma undergone minimally invasive therapy. Chin J Cancer. 2010 Jun;29(6):596-602. doi: 10.5732/cjc.009.10580.
PubMed 20507732Sudo K, Nakamura K, Yamaguchi T. S-1 in the treatment of pancreatic cancer. World J Gastroenterol. 2014 Nov 7;20(41):15110-8. doi: 10.3748/wjg.v20.i41.15110.
PubMed 25386059Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. doi: 10.1200/JCO.2012.43.3680. Epub 2013 Apr 1.
PubMed 23547081Wang Z, Liu Y, Li R, Shang Y, Zhang Y, Zhao L, Li W, Yang Y, Zhang X, Yang T, Nie C, Han F, Liu Y, Luo S, Gao Q, Song Y. Autologous cytokine-induced killer cell transfusion increases overall survival in advanced pancreatic cancer. J Hematol Oncol. 2016 Feb 3;9:6. doi: 10.1186/s13045-016-0237-6.
PubMed 26842696Xie Y, Huang L, Chen L, Lin X, Chen L, Zheng Q. Effect of dendritic cell-cytokine-induced killer cells in patients with advanced colorectal cancer combined with first-line treatment. World J Surg Oncol. 2017 Nov 28;15(1):209. doi: 10.1186/s12957-017-1278-1.
PubMed 29179719Yuan X, Zhang AZ, Ren YL, Wang XL, Jiang CH, Yang L, Liu CX, Liang WH, Pang LJ, Gu WY, Li F, Hu JM. Cytokine-induced killer cells/dendritic cells and cytokine-induced killer cells immunotherapy for the treatment of esophageal cancer: A meta-analysis. Medicine (Baltimore). 2021 Apr 2;100(13):e24519. doi: 10.1097/MD.0000000000024519.
PubMed 33787569
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Controlled Trial Of Dendritic Cell + Cytokine-Induced Killer Cell Immunotherapy With S-1 Versus S-1 Alone As Maintenance Therapy For Advanced Pancreatic Ductal Adenocarcinoma Patients
- ClinicalTrials.gov ID
- NCT05955157
- Acronym / sponsor ID
- DECIMATE 3.0
- Keywords
- Cell-based Immunotherapy, S-1 combined DC+CIK maintenance treatment, DC+CIK immunotherapy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 52 participants (estimated)
- Lead sponsor
- University of MalayaUniversity, hospital or other
- Study start
- 3 Jan 2023 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Jun 2025 (estimated)
- First posted
- 21 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this randomized phase 2 controlled clinical trial is to study safety, efficacy of S-1 combined DC+CIK maintenance therapy compared with S-1 alone in improving clinical benefit rate (CBR) among advanced PDAC patients. The main objectives aim to be achieved through this study are :
- To evaluate the safety of DC+CIK combined immunotherapy when administered with the chemotherapy S-1 as maintenance therapy following first-line chemotherapy regime to advanced pancreatic ductal adenocarcinoma patients.
- To demonstrate the superiority of of DC+CIK combined immunotherapy in improving clinical benefit rate (CBR) of advanced pancreatic ductal adenocarcinoma patients when administered with the chemotherapy S-1 as maintenance therapy following first-line chemotherapy regime.
- To investigate the ability of S-1 combined DC+CIK maintenance therapy in reducing pancreatic ductal adenocarcinoma patients' circulating cancer stem cells (CSCs).
In this study, subjects who achieve at least stable disease or partial response will be randomized in ratio of 1:1 into treatment group: DC-CIK plus S1 (27 patients) and control group: S-1 alone (27 patients). For treatment group, they will be infused with DC first, followed by CIK immune cells on day 1. DC+CIK immunotherapy will be repeated for another 2 times (day 8 and 15) as one cycle. All patients are left to rest for a week (start from day 21) prior to receive another 3 times of infusion (day 28, 35 and 42) if condition allowed. Additional third cycle can be performed on those who tolerate well with no toxicity or respond very well. Patients from treatment group will be assessed for their eligibility to receive booster dose on following conditions: 1) tumour achieves partial response or stable disease and 2) ECOG-PS performance status of 0-2 and 3) doesn't exhibit grade 1 and 2 toxicities to improve tumour control.
Additionally, S-1 will be given twice daily after meals for 2 weeks as first cycle along with DC+CIK. Next second cycle of S-1 will be given after 7-days (1 week) rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent. Dose of S-1 will be determined according to the body surface area.
Meanwhile, patients from control group will receive S-1 alone as maintenance therapy twice daily after meals for 14 days (2 weeks) as one cycle. The next cycle of S-1 will be given after 7-days rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent.
Detailed description
This trial is designed as randomized phase 2 controlled clinical trial.
Subjects who fulfill following inclusion criteria will be admitted to this phase 2 trial and will be excluded if they fulfill any one of the exclusion criteria. All patients must have undergone first-line of chemotherapy (either modified FOLFIRINOX or gemcitabine-based) for at least 3 months and achieved at least stable disease. The inclusion criteria are as follow: 1) histologically and cytologically confirmed advanced pancreatic ductal adenocarcinoma according to AJCC (American Joint Committee on Cancer) TNM system; 2) have undergone first-line of chemotherapy (modified FOLFIRINOX or gemcitabine-based) for at least 3 months and achieved at least stable disease; 3) Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2; 4) age above 18 ages and 5) life expectancy more than three months. Meanwhile, the exclusion criteria are 1) pregnant and lactating women; 2) concomitant beta-adrenergic drug blockers medication; 3) active infection; 4) current enrollment in another clinical study with an investigational agent and 5) patients who undergo pancreas or metastatic site radiotherapy need to be recovered from the toxicities.
Next, patients who achieve at least stable disease will be checked for peripheral blood mononuclear cells (PBMC) adequacy, hematoprofiling using full blood count (FBC) and their baseline status. This is followed by leukapheresis once all conditions satisfied and met. Apheretic products will be sent to local sponsor-contracted laboratory prior for incubation of patients' immune cells with PDAC antigens under specific medium.
All subjects in this trial have been diagnosed with advanced stage of PDAC and being treated with standard chemo: modified FOLFIRINOX or gemcitabine-based regime for at least 3 months. Once the DC+CIK infusion bags are ready to be manufactured, those who achieve at least stable disease or partial response will be randomized in ratio of 1:1 into treatment group: DC-CIK plus S1 (27 patients) and control group: S-1 alone (27 patients).
For treatment group, DC+CIK infusion bag will be administrated right after 17 days patients discharged. Patients will be infused with DC first, followed by CIK immune cells on day 1. DC+CIK immunotherapy will be repeated for another 2 times (day 8 and 15) as one cycle. All patients are left to rest for a week (start from day 21) prior to receive another 3 times of infusion (day 28, 35 and 42) if condition allowed. DC+CIK immunotherapy will be offered as two cycles for every patient in treatment group.
Additional third cycle can be performed on those who tolerate well with no toxicity or respond very well. Patients from treatment group will be assessed for their eligibility to receive booster dose on following conditions: 1) tumour achieves partial response or stable disease and 2) ECOG-PS performance status of 0-2 and 3) doesn't exhibit grade 1 and 2 toxicities to improve tumour control.
Additionally, S-1 will be given twice daily after meals for 2 weeks as first cycle along with DC+CIK. Next second cycle of S-1 will be given after 7-days (1 week) rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent. Dose of S-1 will be determined according to the body surface area.
Meanwhile, patients from control group will receive S-1 alone as maintenance therapy twice daily after meals for 14 days (2 weeks) as one cycle. The next cycle of S-1 will be given after 7-days rest. The cycles will be repeated every 21 days until disease progression, unacceptable toxic effects, or withdrawal with consent.
All patients will be followed up for clinical effects of S-1 combined maintenance therapy translated by tumour best overall response towards the treatment, either complete response (CR), partial response (PR), stable disease (SD) outcomes or progression disease (PD) and level of prognostic biomarkers. Besides, all patients will undergo baseline CT/MRI scan within 4 weeks of patient randomization and before immunotherapy being initiated. This is followed by reassessment CT/MRI scan at the end of 8th weeks starting from date of first treatment, and after S-1 combined DC+CIK immunotherapy completed. All patients will be followed-up regularly to monitor disease progression using reassessment CT/MRI scan at eight weeks interval until first PD observed (Timeframe = 12 months).
Patients' blood will be taken before maintenance treatment initiated and after maintenance treatment completed to evaluate serum cytokine concentration changes and level of circulating cancer stem cells (CSCs). Furthermore, blood will also be taken after each cycle of DC+CIK immunotherapy completed to evaluate baseline peripheral immune profile. Serum CA19-9 concentrations will be monitored every 4 weeks using blood test after first cycle of DC+CIK treatment completed.
Two endoscopic-ultrasound (EUS) guided biopsy pancreatic specimens (optional) will be collected from treatment group patients before maintenance treatment given and after completion of second cycle DC+CIK immunotherapy to quantify tumour-infiltrating lymphocytes (TILs), apoptotic protein expressed on tumour cells and apoptotic cells.
Finally, patients will be monitored for side effects, toxicities and response toward treatment weekly starting on day 7th onward after initial DC+CIK administration. All dated events occurring any time after informed consent will be obtained until 7 days (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Experimental | Biological: Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapy, Drug: Tegafur Only ProductReceiving DC-CIK plus S1 maintenance treatment |
| Control Group | Active comparator | Drug: Tegafur Only ProductReceiving S-1 maintenance treatment alone |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically and cytologically confirmed advanced pancreatic ductal adenocarcinoma according to AJCC (American Joint Committee on Cancer) TNM system;
- Have undergone first-line of chemotherapy (modified FOLFIRINOX or gemcitabine-based) for at least 3 months and achieved at least stable disease;
- Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2;
- Age above 18 ages
- Life expectancy more than three months.
Key exclusion criteria (5 listed)
- Pregnant and lactating women
- Concomitant beta-adrenergic drug blockers medication
- Active infection
- Current enrollment in another clinical study with an investigational agent
- Patients who undergo radiotherapy to pancreas or metastatic site need to be recovered from the toxicities
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapyDC+CIK immunotherapy will be administrated with S-1 chemo drug as maintenance treatment for patients with advanced PDAC | Biological | Treatment Group |
| Tegafur Only ProductTegafur (TS-1) will be administrated alone as maintenance treatment to control group as standard of care | Drug | Control Group, Treatment Group |
Primary outcome
Number of participants with treatment-related adverse events
Time frame: 3 months
Safety of patients towards treatment will be evaluated based on number of adverse events (AEs) and serious adverse events (SAEs) reported.
Incidence of treatment-emergent hematologic side effects
Time frame: 3 months
Feasibility of experimental treatment will be evaluated based on result of differential complete blood count.
2 secondary outcomes
Clinical benefit rate (CBR) - Change from baseline in tumour burden
Time frame: 12 months
Efficacy of S-1 combined DC+CIK in controlling tumour
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
- Background: PubMed 32946773Bear AS, Vonderheide RH, O'Hara MH. Challenges and Opportunities for Pancreatic Cancer Immunotherapy. Cancer Cell. 2020 Dec 14;38(6):788-802. doi: 10.1016/j.ccell.2020.08.004. Epub 2020 Sep 17.
- Background: PubMed 26565954Chen L, Zhang X. Primary analysis for clinical efficacy of immunotherapy in patients with pancreatic cancer. Immunotherapy. 2016 Feb;8(2):223-34. doi: 10.2217/imt.15.105. Epub 2015 Nov 13.
- Background: PubMed 32345239Du H, Yang J, Zhang Y. Cytokine-induced killer cell/dendritic cell combined with cytokine-induced killer cell immunotherapy for treating advanced gastrointestinal cancer. BMC Cancer. 2020 Apr 28;20(1):357. doi: 10.1186/s12885-020-06860-y.
- Background: PubMed 19097774Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
- Background: PubMed 26723878Foley K, Kim V, Jaffee E, Zheng L. Current progress in immunotherapy for pancreatic cancer. Cancer Lett. 2016 Oct 10;381(1):244-51. doi: 10.1016/j.canlet.2015.12.020. Epub 2015 Dec 23.
- Background: PubMed 23794732Gammaitoni L, Giraudo L, Leuci V, Todorovic M, Mesiano G, Picciotto F, Pisacane A, Zaccagna A, Volpe MG, Gallo S, Caravelli D, Giacone E, Venesio T, Balsamo A, Pignochino Y, Grignani G, Carnevale-Schianca F, Aglietta M, Sangiolo D. Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features. Clin Cancer Res. 2013 Aug 15;19(16):4347-58. doi: 10.1158/1078-0432.CCR-13-0061. Epub 2013 Jun 21.
- Background: PubMed 28760152Haag GM, Stocker G, Quidde J, Jaeger D, Lordick F. Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer - the multinational MATEO study. BMC Cancer. 2017 Jul 31;17(1):509. doi: 10.1186/s12885-017-3497-9.
- Background: PubMed 29461610He W, Huang Z, Zhou S, Huang L, Wang B, Zhu L, Ding Y, Yu YL, Zhang S. The effect of DC+CIK combined therapy on rat liver cancer model and its modulatory effect on immune functions. Eur Rev Med Pharmacol Sci. 2018 Feb;22(3):778-785. doi: 10.26355/eurrev_201802_14312.
- Background: PubMed 32940362Miller KD, Fidler-Benaoudia M, Keegan TH, Hipp HS, Jemal A, Siegel RL. Cancer statistics for adolescents and young adults, 2020. CA Cancer J Clin. 2020 Nov;70(6):443-459. doi: 10.3322/caac.21637. Epub 2020 Sep 17.
- Background: PubMed 20507732Pan CC, Huang ZL, Li W, Zhao M, Zhou QM, Xia JC, Wu PH. Serum alpha-fetoprotein measurement in predicting clinical outcome related to autologous cytokine-induced killer cells in patients with hepatocellular carcinoma undergone minimally invasive therapy. Chin J Cancer. 2010 Jun;29(6):596-602. doi: 10.5732/cjc.009.10580.
- Background: PubMed 25386059Sudo K, Nakamura K, Yamaguchi T. S-1 in the treatment of pancreatic cancer. World J Gastroenterol. 2014 Nov 7;20(41):15110-8. doi: 10.3748/wjg.v20.i41.15110.
- Background: PubMed 23547081Ueno H, Ioka T, Ikeda M, Ohkawa S, Yanagimoto H, Boku N, Fukutomi A, Sugimori K, Baba H, Yamao K, Shimamura T, Sho M, Kitano M, Cheng AL, Mizumoto K, Chen JS, Furuse J, Funakoshi A, Hatori T, Yamaguchi T, Egawa S, Sato A, Ohashi Y, Okusaka T, Tanaka M. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640-8. doi: 10.1200/JCO.2012.43.3680. Epub 2013 Apr 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dendritic cell + Cytokine-induced killer cell (DC+CIK) immunotherapy and Tegafur Only Product in people with Pancreatic Ductal Adenocarcinoma and Advanced Solid Tumor, run by University of Malaya at 1 site in Malaysia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malaysia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact HO GWO FUANG, MBBS (03-79492120, gwoho@um.edu.my), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05955157, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2024.