search
Back to results

Sintilimab Combined With Chemotherapy and Radiotherapy in Patients With Inoperable Pancreatic Cancer

Primary Purpose

Pancreas Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Sintilimab Plus mFFN and Radiation
Sponsored by
Shandong Cancer Hospital and Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreas Cancer focused on measuring Immunothrapy, Chemotherapy, Radiothrapy, Pancreatic cancer

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: ECOG PS 0-1 Pathological tissue-confirmed unresectable locally advanced pancreatic cancer Pancreatic cancer patients who have not received systemic anti-tumor therapy Primary pancreatic cancer or at least one measurable lesion specified by RECIST1.1 standards A life expectancy of > 3 months Blood routine examination: Absolute neutrophil count (ANC) ≥ 1.0 ×109 cells/L, platelets ≥ 75×109 cells/L, hemoglobin ≥ 9.0 g/dl AST<2.5 × ULN(Upper Limit of Normal), ALT<2.5 × ULN,creatinine ≤1.5xULN, total bilirubin < ≤1.5 X ULN. Exclusion Criteria: Diagnosed with other malignant diseases other than pancreatic cancer within three years before enrollment Patients who are currently participating in interventional clinical research treatment or have received other research drugs or used research devices within four weeks before enrollment Patients who have previously received anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or another drug that stimulates or synergistically inhibits T-cell receptors Patients who have received systemic treatment with Chinese patent medicines with anti-tumor indications or drugs with immunomodulatory effects within two weeks before enrollment Abnormal results of blood routine examinations and liver and kidney and coagulation tests Abnormal function of major organs (14 days before enrollment) Women who are pregnant Inability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.

Sites / Locations

  • Department of Radiation Oncology, Shandong Cancer Hospital and InstituteRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sintilimab Plus Chemotherapy and Radiotherapy

Arm Description

Sintilimab Plus mFFN and Radiation

Outcomes

Primary Outcome Measures

PFS
Time from first dose of study drug to first radiographic disease progression or death, whichever occurs first
AE
Advent event rate

Secondary Outcome Measures

Overal response rate
Proportion of subjects with complete response (CR) and partial response (PR) to total subjects; including assessment of irradiated lesions and non-irradiated lesions
Overall survival
The time from the start of treatment to death
Disease control rate
Proportion of total subjects defined as complete response (CR), partial response (PR), and stable disease (SD)
Duration of response
The time from when the tumor is first evaluated as CR or PR to when the tumor is first evaluated as PD (Progressive Disease) or death from any cause

Full Information

First Posted
September 17, 2023
Last Updated
September 21, 2023
Sponsor
Shandong Cancer Hospital and Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT06050317
Brief Title
Sintilimab Combined With Chemotherapy and Radiotherapy in Patients With Inoperable Pancreatic Cancer
Official Title
Sintilimab Plus Chemotherapy and Radiotherapy for Patients With Inoperable Pancreatic Cancer: a Single-arm, Exploratory, Phase II Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 18, 2023 (Actual)
Primary Completion Date
August 18, 2025 (Anticipated)
Study Completion Date
August 18, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shandong Cancer Hospital and Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Hypothesis: Survival benefits could be found in Sintilimab plus chemotherapy and radiotherapy in patients with inoperable pancreatic cancer.
Detailed Description
Background and aim: Pancreatic cancer, characterized by its aggressive nature and dismal prognosis, exhibits one of the lowest 5-year survival rates among all solid tumors, standing at a mere 7%. Alarming projections suggest that by the year 2030, it will ascend to become the second leading cause of cancer-related deaths. This dire scenario is further compounded by the stealthy onset of the disease, with an overwhelming 80-85% of patients already presenting with unresectable pancreatic cancer at the time of initial diagnosis. Clinical trials have endeavored to extend the survival of this challenging patient subset through the administration of chemotherapy or chemoradiotherapy. While these interventions have shown some promise, the overall response rate remains disappointingly low, and patients continue to grapple with a bleak prognosis, often surviving less than a year. This unmet medical need underscores the critical demand for more effective therapeutic modalities in the management of pancreatic cancer, as the lack of viable treatment options remains a primary driver of its high mortality rate. The traditional therapeutic landscape for unresectable pancreatic cancer primarily relies on single-agent chemotherapy. However, there is a growing realization within the medical community that a paradigm shift toward a multidisciplinary approach is imperative. The crux of achieving long-term survival for pancreatic cancer patients lies in the attainment of a durable anti-tumor response. Targeted PD-(L)1 immunotherapy, renowned for its ability to induce enduring anti-tumor responses by harnessing the body's own immune system, has yielded remarkable results in various malignancies. Paradoxically, the success of single-agent immunotherapy in pancreatic cancer has been elusive, a phenomenon possibly attributed to the tumor's intrinsic genetic mutations and the hostile, immunosuppressive microenvironment that envelops pancreatic tumors. Radiation therapy has emerged as a potential ally in this battle against pancreatic cancer. It has been demonstrated to augment the release of tumor-associated antigens, thereby priming the immune system for a more robust response. In response to the resistance encountered with PD-(L)1 monotherapy, researchers have embarked on a journey of preclinical and clinical investigations aimed at validating the combinatorial approach of PD-(L)1 inhibitors alongside chemotherapy and radiation therapy. The fundamental premise underlying the synergy of radiation and immunotherapy is rooted in the non-invasive initiation of the immune system against tumor cells. Radiation serves as a catalyst, promoting antigen presentation and co-stimulation, culminating in the generation of an immune response targeted at epitopes that had remained concealed within distant metastases. Immune checkpoint inhibitors play a pivotal role in reversing the immunosuppressive effects of the tumor microenvironment, thereby fostering a milieu conducive to anti-tumor immunity. While the efficacy of this integrative approach remains uncharted territory, current recommendations advocate for a first-line treatment strategy consisting of chemotherapy with optional radiation therapy. Targeted therapy and immunotherapy are not currently included in the initial treatment regimen. Consequently, the primary aim of our study is to explore and elucidate the outcomes of combining Sintilimab with radiation therapy and chemotherapy in the treatment of unresectable pancreatic cancer, offering a glimmer of hope in a landscape fraught with challenges and adversity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreas Cancer
Keywords
Immunothrapy, Chemotherapy, Radiothrapy, Pancreatic cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Sintilimab Plus Chemotherapy and Radiotherapy
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Sintilimab Plus Chemotherapy and Radiotherapy
Arm Type
Experimental
Arm Description
Sintilimab Plus mFFN and Radiation
Intervention Type
Drug
Intervention Name(s)
Sintilimab Plus mFFN and Radiation
Other Intervention Name(s)
Arm
Intervention Description
Sintilimab Plus mFFN and Radiation
Primary Outcome Measure Information:
Title
PFS
Description
Time from first dose of study drug to first radiographic disease progression or death, whichever occurs first
Time Frame
2 year
Title
AE
Description
Advent event rate
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Overal response rate
Description
Proportion of subjects with complete response (CR) and partial response (PR) to total subjects; including assessment of irradiated lesions and non-irradiated lesions
Time Frame
2 year
Title
Overall survival
Description
The time from the start of treatment to death
Time Frame
2 year
Title
Disease control rate
Description
Proportion of total subjects defined as complete response (CR), partial response (PR), and stable disease (SD)
Time Frame
2 year
Title
Duration of response
Description
The time from when the tumor is first evaluated as CR or PR to when the tumor is first evaluated as PD (Progressive Disease) or death from any cause
Time Frame
2 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ECOG PS 0-1 Pathological tissue-confirmed unresectable locally advanced pancreatic cancer Pancreatic cancer patients who have not received systemic anti-tumor therapy Primary pancreatic cancer or at least one measurable lesion specified by RECIST1.1 standards A life expectancy of > 3 months Blood routine examination: Absolute neutrophil count (ANC) ≥ 1.0 ×109 cells/L, platelets ≥ 75×109 cells/L, hemoglobin ≥ 9.0 g/dl AST<2.5 × ULN(Upper Limit of Normal), ALT<2.5 × ULN,creatinine ≤1.5xULN, total bilirubin < ≤1.5 X ULN. Exclusion Criteria: Diagnosed with other malignant diseases other than pancreatic cancer within three years before enrollment Patients who are currently participating in interventional clinical research treatment or have received other research drugs or used research devices within four weeks before enrollment Patients who have previously received anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or another drug that stimulates or synergistically inhibits T-cell receptors Patients who have received systemic treatment with Chinese patent medicines with anti-tumor indications or drugs with immunomodulatory effects within two weeks before enrollment Abnormal results of blood routine examinations and liver and kidney and coagulation tests Abnormal function of major organs (14 days before enrollment) Women who are pregnant Inability of the research subject or authorized legal representative to understand and the willingness to sign a written informed consent document.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jinbo Yue, dorctor
Phone
0531-67626442
Email
yuejinbo@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Xu, dorctor
Phone
0531-67626442
Email
Len.Xu@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinbo Yue, dorctor
Organizational Affiliation
Shandong Cancer Hospital and Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Radiation Oncology, Shandong Cancer Hospital and Institute
City
Jinan
State/Province
Shandong
ZIP/Postal Code
0531
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jinbo Yue, doctor
Phone
0531-67626442
Email
yuejinbo@hotmail.com

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
27956793
Citation
Ilic M, Ilic I. Epidemiology of pancreatic cancer. World J Gastroenterol. 2016 Nov 28;22(44):9694-9705. doi: 10.3748/wjg.v22.i44.9694.
Results Reference
background
PubMed Identifier
24840647
Citation
Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155. Erratum In: Cancer Res. 2014 Jul 15;74(14):4006.
Results Reference
background
PubMed Identifier
26491905
Citation
Strohl MP, Raigani S, Ammori JB, Hardacre JM, Kim JA. Surgery for Localized Pancreatic Cancer: The Trend Is Not Improving. Pancreas. 2016 May-Jun;45(5):687-93. doi: 10.1097/MPA.0000000000000511.
Results Reference
background
PubMed Identifier
21561347
Citation
Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardiere C, Bennouna J, Bachet JB, Khemissa-Akouz F, Pere-Verge D, Delbaldo C, Assenat E, Chauffert B, Michel P, Montoto-Grillot C, Ducreux M; Groupe Tumeurs Digestives of Unicancer; PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011 May 12;364(19):1817-25. doi: 10.1056/NEJMoa1011923.
Results Reference
background
PubMed Identifier
9196156
Citation
Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997 Jun;15(6):2403-13. doi: 10.1200/JCO.1997.15.6.2403.
Results Reference
background
PubMed Identifier
24131140
Citation
Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
Results Reference
background
PubMed Identifier
17560615
Citation
Fukumura D, Jain RK. Tumor microvasculature and microenvironment: targets for anti-angiogenesis and normalization. Microvasc Res. 2007 Sep-Nov;74(2-3):72-84. doi: 10.1016/j.mvr.2007.05.003. Epub 2007 May 18.
Results Reference
background
PubMed Identifier
28576181
Citation
Badiyan SN, Molitoris JK, Chuong MD, Regine WF, Kaiser A. The Role of Radiation Therapy for Pancreatic Cancer in the Adjuvant and Neoadjuvant Settings. Surg Oncol Clin N Am. 2017 Jul;26(3):431-453. doi: 10.1016/j.soc.2017.01.012. Epub 2017 May 11.
Results Reference
background
PubMed Identifier
33772154
Citation
Auclin E, Marthey L, Abdallah R, Mas L, Francois E, Saint A, Cunha AS, Vienot A, Lecomte T, Hautefeuille V, de La Fouchardiere C, Sarabi M, Ksontini F, Forestier J, Coriat R, Fabiano E, Leroy F, Williet N, Bachet JB, Tougeron D, Taieb J. Role of FOLFIRINOX and chemoradiotherapy in locally advanced and borderline resectable pancreatic adenocarcinoma: update of the AGEO cohort. Br J Cancer. 2021 Jun;124(12):1941-1948. doi: 10.1038/s41416-021-01341-w. Epub 2021 Mar 26.
Results Reference
background
PubMed Identifier
21969502
Citation
Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011 Nov 1;29(31):4105-12. doi: 10.1200/JCO.2011.34.8904. Epub 2011 Oct 3.
Results Reference
background
PubMed Identifier
18467316
Citation
Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, Bosset JF, Aparicio T, Mineur L, Azzedine A, Hammel P, Butel J, Stremsdoerfer N, Maingon P, Bedenne L. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000-01 FFCD/SFRO study. Ann Oncol. 2008 Sep;19(9):1592-9. doi: 10.1093/annonc/mdn281. Epub 2008 May 7.
Results Reference
background
PubMed Identifier
27139057
Citation
Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, Borbath I, Bouche O, Shannon J, Andre T, Mineur L, Chibaudel B, Bonnetain F, Louvet C; LAP07 Trial Group. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. JAMA. 2016 May 3;315(17):1844-53. doi: 10.1001/jama.2016.4324.
Results Reference
background
PubMed Identifier
2864997
Citation
Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer. 1985 Dec 1;56(11):2563-8. doi: 10.1002/1097-0142(19851201)56:113.0.co;2-0.
Results Reference
background
PubMed Identifier
28708929
Citation
de Geus SWL, Eskander MF, Kasumova GG, Ng SC, Kent TS, Mancias JD, Callery MP, Mahadevan A, Tseng JF. Stereotactic body radiotherapy for unresected pancreatic cancer: A nationwide review. Cancer. 2017 Nov 1;123(21):4158-4167. doi: 10.1002/cncr.30856. Epub 2017 Jul 14.
Results Reference
background
PubMed Identifier
32125712
Citation
Tchelebi LT, Lehrer EJ, Trifiletti DM, Sharma NK, Gusani NJ, Crane CH, Zaorsky NG. Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): An international systematic review and meta-analysis. Cancer. 2020 May 15;126(10):2120-2131. doi: 10.1002/cncr.32756. Epub 2020 Mar 3.
Results Reference
background
PubMed Identifier
33630475
Citation
Hewitt DB, Nissen N, Hatoum H, Musher B, Seng J, Coveler AL, Al-Rajabi R, Yeo CJ, Leiby B, Banks J, Balducci L, Vaccaro G, LoConte N, George TJ, Brenner W, Elquza E, Vahanian N, Rossi G, Kennedy E, Link C, Lavu H. A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects With Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. Ann Surg. 2022 Jan 1;275(1):45-53. doi: 10.1097/SLA.0000000000004669.
Results Reference
background
PubMed Identifier
31439714
Citation
Ahmad G, Mackenzie GG, Egan J, Amiji MM. DHA-SBT-1214 Taxoid Nanoemulsion and Anti-PD-L1 Antibody Combination Therapy Enhances Antitumor Efficacy in a Syngeneic Pancreatic Adenocarcinoma Model. Mol Cancer Ther. 2019 Nov;18(11):1961-1972. doi: 10.1158/1535-7163.MCT-18-1046. Epub 2019 Aug 22.
Results Reference
background
PubMed Identifier
29119276
Citation
Weiss GJ, Blaydorn L, Beck J, Bornemann-Kolatzki K, Urnovitz H, Schutz E, Khemka V. Phase Ib/II study of gemcitabine, nab-paclitaxel, and pembrolizumab in metastatic pancreatic adenocarcinoma. Invest New Drugs. 2018 Feb;36(1):96-102. doi: 10.1007/s10637-017-0525-1. Epub 2017 Nov 8. Erratum In: Invest New Drugs. 2019 Aug;37(4):797.
Results Reference
background
PubMed Identifier
35662283
Citation
Padron LJ, Maurer DM, O'Hara MH, O'Reilly EM, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Yu JX, Pfeiffer SM, Spasic M, Xu J, Gherardini PF, Karakunnel J, Mick R, Alanio C, Byrne KT, Hollmann TJ, Moore JS, Jones DD, Tognetti M, Chen RO, Yang X, Salvador L, Wherry EJ, Dugan U, O'Donnell-Tormey J, Butterfield LH, Hubbard-Lucey VM, Ibrahim R, Fairchild J, Bucktrout S, LaVallee TM, Vonderheide RH. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022 Jun;28(6):1167-1177. doi: 10.1038/s41591-022-01829-9. Epub 2022 Jun 3.
Results Reference
background
PubMed Identifier
28493288
Citation
Zhong J, Patel K, Switchenko J, Cassidy RJ, Hall WA, Gillespie T, Patel PR, Kooby D, Landry J. Outcomes for patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiation therapy versus conventionally fractionated radiation. Cancer. 2017 Sep 15;123(18):3486-3493. doi: 10.1002/cncr.30706. Epub 2017 May 10.
Results Reference
result
PubMed Identifier
36592507
Citation
Chen IM, Donia M, Chamberlain CA, Jensen AWP, Draghi A, Theile S, Madsen K, Hasselby JP, Toxvaerd A, Hogdall E, Lorentzen T, Wilken EE, Geertsen P, Svane IM, Johansen JS, Nielsen D. Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R). Eur J Cancer. 2023 Feb;180:125-133. doi: 10.1016/j.ejca.2022.11.035. Epub 2022 Dec 10.
Results Reference
result
PubMed Identifier
34237249
Citation
Zhu X, Cao Y, Liu W, Ju X, Zhao X, Jiang L, Ye Y, Jin G, Zhang H. Stereotactic body radiotherapy plus pembrolizumab and trametinib versus stereotactic body radiotherapy plus gemcitabine for locally recurrent pancreatic cancer after surgical resection: an open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2021 Aug;22(8):1093-1102. doi: 10.1016/S1470-2045(21)00286-2. Epub 2021 Jul 5.
Results Reference
result
PubMed Identifier
35476508
Citation
Chen IM, Johansen JS, Theile S, Hjaltelin JX, Novitski SI, Brunak S, Hasselby JP, Willemoe GL, Lorentzen T, Madsen K, Jensen BV, Wilken EE, Geertsen P, Behrens C, Nolsoe C, Hermann KL, Svane IM, Nielsen D. Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC). J Clin Oncol. 2022 Sep 20;40(27):3180-3189. doi: 10.1200/JCO.21.02511. Epub 2022 Apr 27.
Results Reference
result

Learn more about this trial

Sintilimab Combined With Chemotherapy and Radiotherapy in Patients With Inoperable Pancreatic Cancer

We'll reach out to this number within 24 hrs