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

Sponsor

Shandong Cancer Hospital and Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT06050317

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Hypothesis: Survival benefits could be found in Sintilimab plus chemotherapy and radiotherapy in patients with inoperable pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreas Cancer	Drug: Sintilimab Plus mFFN and Radiation	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Sintilimab Plus Chemotherapy and RadiotherapySintilimab Plus Chemotherapy and Radiotherapy

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sintilimab Plus Chemotherapy and Radiotherapy for Patients With Inoperable Pancreatic Cancer: a Single-arm, Exploratory, Phase II Trial

Actual Study Start Date :

Aug 18, 2023

Anticipated Primary Completion Date :

Aug 18, 2025

Anticipated Study Completion Date :

Aug 18, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sintilimab Plus Chemotherapy and Radiotherapy Sintilimab Plus mFFN and Radiation	Drug: Sintilimab Plus mFFN and Radiation Sintilimab Plus mFFN and Radiation Other Names: Arm

Arm

Intervention/Treatment

Experimental: Sintilimab Plus Chemotherapy and Radiotherapy

Sintilimab Plus mFFN and Radiation

Drug: Sintilimab Plus mFFN and Radiation

Sintilimab Plus mFFN and Radiation

Other Names:

Arm

Outcome Measures

Primary Outcome Measures

PFS [2 year]
Time from first dose of study drug to first radiographic disease progression or death, whichever occurs first
AE [2 year]
Advent event rate

Secondary Outcome Measures

Overal response rate [2 year]
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 [2 year]
The time from the start of treatment to death
Disease control rate [2 year]
Proportion of total subjects defined as complete response (CR), partial response (PR), and stable disease (SD)
Duration of response [2 year]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Radiation Oncology, Shandong Cancer Hospital and Institute	Jinan	Shandong	China	0531

Sponsors and Collaborators

Shandong Cancer Hospital and Institute

Investigators

Principal Investigator: Jinbo Yue, dorctor, Shandong Cancer Hospital and Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Jinbo Yue, Jinbo Yue, Shandong Cancer Hospital and Institute

ClinicalTrials.gov Identifier:

NCT06050317

Other Study ID Numbers:

SDZLEC2023-227-02

First Posted:

Sep 22, 2023

Last Update Posted:

Sep 22, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Jinbo Yue, Jinbo Yue, Shandong Cancer Hospital and Institute

Additional relevant MeSH terms:

Pancreatic Neoplasms

Study Results

No Results Posted as of Sep 22, 2023